HUE029811T2 - Szelenitet vagy szelenit-tartalmú vegyületet tartalmazó gyógyszerkészítmény méhnyak-diszpláziák vagy -karcinómák kezelésére - Google Patents
Szelenitet vagy szelenit-tartalmú vegyületet tartalmazó gyógyszerkészítmény méhnyak-diszpláziák vagy -karcinómák kezelésére Download PDFInfo
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- HUE029811T2 HUE029811T2 HUE12707218A HUE12707218A HUE029811T2 HU E029811 T2 HUE029811 T2 HU E029811T2 HU E12707218 A HUE12707218 A HU E12707218A HU E12707218 A HUE12707218 A HU E12707218A HU E029811 T2 HUE029811 T2 HU E029811T2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
- A61K9/0036—Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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Description
PHARMACEUTICAL PREPARAT 1 OU CONTAINING SELENITE OR SELENITE ~ CONTAIN ING COMPOUNDS FOR THE TR^TMENT OF CERVICAL DTSELMlM OR CARCINOMAS
The present invention relates to pharmaceutical compositions containing selenite-containing compounds.
Inflammatory and/or degenerative alterations of the female cervix are a steadily increasing public health problem. Testing of cervical ceil smears sas developed by the Greek physician George Papanicolaou and the shears are olasoi tied according to the so-called Munich nomenclature II. Herein, the classification PAP I corresponds to a normal result, PAP II to a minor inflammatory and/or degenerative alteration, PAP XIX to ceil profiles that cannot be assessed, and need to be monitored, PA? HID to a dysplasia, PAP IV to serious preliminary stages of carcinoma, and PAP V to a malign tumor. The forms of dysplasia PAP HID and PAP IV are cytologicaily further differentiated into so-called "servi cal intraepithelial neopLasias" (CIN) with the stages of CIN 1 for minor, CIH 2 for moderate, and CIN 3 for severe dysplasia. Analogously to the histological classification from CIN 1 (PAP HID) to CIN 2 (also PAP HID} to CIN 3 (PAP IV.),. it is also referred to the so-called Bethesda classification in the Anglo-American part of the world. Herein, the ’’Low-Grade Squamous Intraepithelial Lesion ’’ (LSIL) corresponds to the Munich classification CIN 1, whereas cell alterations of a higher grade, i, s, ’’High-Grade Squamous Intraepithelial Lesions'’ {HSÏL) , correspond to the WHO olassif i eat ions CIN /. and CIN 3.
The average tendency for the regression of minor dysplasias (PAP HID / CIN 1 / LaDL): to a normal result (PAP I and PAP II, respectively) within a onb-ysar period is as low as almost 151, The tendency for the progression of minor dysplasias (PAP HID / CIN 1 / LSIL} to higher-grade dysplasias currently exhibits a mean annual transition probability of more than 7%, while the progression tendency of higher-grade dysplasias to carcinomas of the uterus is: 0,74%.
Depending on the location and the severity of the cell alterations, the currant inrernationa I g yne colo g icaI quidelin e s for the therapy of Cervical Intraepithelial Neoplasias (CIN) and mi orocarcinemas of the Cervix uteri comprise a destruction of the surface of tbc affected tisses, a conization with the aid of a scalpel, laser or LEE? {Loop Electrosurgieal Erei sión Procedure; or a hysterectomy. Otter non·" sure leal therapies axe not known to date.
On the electrochemical level, inflatniatory tissue processes are always associated with a (local; increase lb so-called Peective Oxygen Species (EOS;, i. e. free radicals and peroxides. In the context of a spontaneous amelioration of these oxidative inf i arena for y factors, the competence of the body's own immune system and the levels of endogenous and exogenous antioxidants an the body play am important biological role. The anti-infiamm&tory and antiviral effects of ant xoxidat i ve ccmposi tiers have already been verified in numerous scientific puni rca tiens and international patent documents (i. a, no 2001/093910 A2 and WO 20037012004 hi) .
It was the object of the present invention to provide new means for the prevention and treatment of inflammations, dysplasias and/or carcinomas of the cervix.
Accordingly, the present invent ion relates to a pharmaceutical composition containing selenite-containing compounds and pharmaceutically acceptable acids, sei acted from citric acid, acetic acid, malic acid, carbonic acid, sulfuric acid, nitric acid, hydrochloric acid, fruit acids (e. g, malic acid, citric acid, tartaric acid, oxalic acid and fumarie acid, in particular citric acid) or arixtures thereof, for use in the treatment of inf latmations, dysplasias arc/or carcinomas of the cervix, wherein said compos it 1 on is used for the treatment of cervical cell a i torstloos having a PAP score of 1 PAP III and/or a CIN score of 1 CIN 1.,
in the context of the present invention, if could surprisingly be found that a consequent Ideal administration of antioxidative selenium-containing preparations (according to NO 2001/093310 A2 and WÖ 2003/047604 11} in vivo also has at positive influence on negative ceil alterations (dysplasias and carcinomas) within the scope of an early detection of cervical carcinoma- The present invention is suitable for both HPV-induced and non-HPV-induced disorders of the uterus. This is of great practical sign!ficance as the detection, or even specification, of the HPV is often omitted in gynecological practice because the positive detection of an HPV infection often has no influence on subsequent therapeutic decisions. However, the inventive treatment of non-HPV-induced uterine disorders (i. e. the use of the preparations according to the present invention in the treatment, of or as a medication for infiabunations> dysplasias and/or carcinomas of the cervix} is a particularly preferred embodiment of the present invention. Consequently, the present invention does not represent a strategy that is directed against a specific pathogen, but rather aims at a treatment of inflammations, dysplasias and/or carcinomas of the cervix in a directed manner, 1. e. ip may also be employed (long; after a potential pathogen has elicited the symptoms of a disease.
If has shorn that a compositeon having an enhanced antioxidative potential may be provided by adding the above-mentioned acids to aqueous solutions of inorganic selenium compounds. Herei a, the compositions prepared according to the present invention, i, e, in particular solutions, gels, emulsions, suspensions, ci nouants and the like, exhibit the therapeutic effects according to the present invention as - owing to the presence of the acids - they may be used in accordance with the present invention such as to, at least temporarily, maintain said enhanced antioxidative potential. This is the case if the enhanced antioxidative potential is still present at the time of administration at the therapy target destination and has not already been diluted, e. g. by administration· solutions or body fluids, such as blood (e, q> in case of intravenous administration) or contents of the digestive: tract (e. g. in case of oral application),
Accordingly, the present invention preferably relates to the topical, mucosa) and intravaginal administration of these preparations for external use (i, e, topical or buccal) or for the direct administration to mucous membranes (mucosal application)-Typical formulations tor administration that are suitable for a topical, mucosal or intravaginai administrâtion are known to a person skilled in the art and have been described in the relevant pharmacopoeias.
In addition to the essential ingredients of selenite and the above-mentioned acids, the composition according to the present invention bey also conto in further suitable ingredients and/or pharmaceutically acceptable excipients, The composition according to the present invention preferably contains selenite in an amount between 1 end 500 mg, mere preferably between 10 end 100 mg, in particular between 30 and 7Ö mg, per 100 g of the composition. Preferably, the composition according to the present intention contains selenite in the form of sodium selenite (which is mostly present as a pentarme rate compound which starts to release crystal water at i0*C}.
Independently^ tbs composition according to the present invention preferably contains one or more acids in a total amount between 1 mg and 10 g acid, more preferably between 10 mg and 5 g acid, in particular between 100 mg and X g acid, per 100 g of the composition (in particular if the acid is added in its solid form;. alternatively, the acid may also be added in its liquid form (e, g. with water, i. e. as an aqueous solution). Water and aqueous solutions, respewlively, optionally containing further ingredients, may be added to the composition according to the present invention in an amount between 0 and (about) 99,9 g„ preferably between 50 and 99 g, in particular between 80 and 88g, per ICO g of the composition,
According to a preferred embodiment, the present invention Is provided in the form of a gel. Accordingly, the composition according to the present invention preferably contains a gelling agent, Both inorganic and organic aqueous gelling agents may be used as a gelling agent. Particularly suitable gelling agents are ceil close dérivâtivesy in part icular oarboxymethyloellulose, methyleellulose, hydrexypropylcellulose and, in particular, hydroxyéthylcelluiôse, breferabiy, the gelling agents, in particular hydroxyethylcelluiose, are used at a total concentration of between 0,1 g and 30 q, more preferably between Ö.3 g and 5 g, in particular between 1 g and 3 g, per 100 g of the composition. A particularly preferred embodiment of the gel composition according to the present invention contains silicon dioxide, in particular highly dispersed silicon dioxide, e. g, according to WO 2001/8 5852 Ai, as a technological suspension medium and/or as an adsorbent. Preferably, an amount between 100 mg and 50 g, more preferably between 500 mg and 10 g, in per tier! nr between 1. g and 5 g, Si Co per 100 g of thé composition is us ecu
The composition acsordino to the present invention preferably has a pH-value: of leas than 1.0, more preferably less than 5 < 0 f in particular between 4,0 and 2,5.
The composition according to the present invention is preferably present in the form of a solution, emulsion, ointment or sponge (tampon;, ncrantageousiy, tbs composlt ton may contain further excipients and/or forther active ingredients, in particular buffer substances, coloring agents, stabilisers, preservatives, carrier substances or combinations thereof. Preferred examples of such substances ara maltodextrin, flavoring agents, such as e. g. lemon flavor, peppermint oil, potassium sor bare and sodium bermsate (as preservatives), and the like.
Prefer red further active ingredients are antibiotics, antiviral agents, arrtimycotics, pain inhibitors, antx-ini 1 ammatc·;y agents or combinations thereof.
The composit ion accord!ng to the present invention has surprisingly proved to be particularly effective in the treatment of cervical cell alterations having a PAP score of a pap m and/or a CIN score of . 1 CIN 1. In particular, the present invention may be used in the treatment of cervical inf la iota fions having a PAP score of PAP 111 and PAP HID,
Pert her more, it is to be pointed out that the present invention is suitable far the treatment of cervical carcinomas, .According: to a further aspect, the present invention relates to a method for the treatment of infsommations, dysplasias and/or carer nomas of the cervix. In which thé compositions according to the present invention are administered in an effective amount to patients suffering from the above disorders. Preferred dosages may range (e. g. when present as a gel) between 0,005 g and 0<i g of sodium selenite paht a hydrate per 100 g of the gel, in particular between 0,01 g and 0.1 g per i()0 g of the gel.
The present invention will be explained in more detail by way of the following Examples, without being limited thereto.
Example It Preparation of an acidified sodium selenite gel An acidified sodium: selenite gel was prepared in the
Loi levying composition (por 100 g; :
Sodium selenite pentahydrate 0.000 g
Silicon dioxide, highly dispersed 0.200 g
Citric acid 0.496 g
Sodium foensoate 0.050 g rot a satuin sor bate 0 ., 0 9 9 q
Hydr ox ys thy1ce11u1o s c 1.9 B S q deter 97.120 g 100,000 g
Exemple 2 : Treairent of cervical dysplasias
Design; Haiti center pilot study
Inclusion criteria; age > 19 years
PAD > Ol < IV
Implementation:
Intravaginal earn n :.strut 1 on of 5 mi of sodium selenite gel 1 2; per day in case of a diagnosis of DAP A III < P·/ over a period of 90 days. The administration is to be discontinued during menstruation. Pci low-up examination after 90 days of gel a dm i n i s t r a t i ο n ,
Sesuits ;
Of 31 patients 2? (87,11) exhibited a response; 4 patients ; 1.2.9%) were non- responders . example 3 : Effects of the acidified sodium selenite gel
First last ext me kpv w
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Yf 32 19.00.2010 11.11.2010 III II n. ft. n,a, KP 67 10.06.2010 03.11.2010 111 IX nag, v.ft. KK 13 24.06,2010 20.09.2010 III XI nag. «eg. CS 50 30.06.2010 08,11,2010 111 111 a.ft. n.a. ML 28 03,06.2010 08.11,2010 1X1 Π aaa. IP 48 10,06.2010 11 .1 1.2010 HX D II pea. n.a. CD 44 07.09.20X0 14.12.2010 III D II aaa. a.ft, KM 21 12.00.20X8 30.11,2010 HI D III D nos. n.d, H 32 13.88.2810 18.11,28X0 XXX II n.d. n.d, £3 38 10,08.201ft 21.09.2010 JXX IX n.d. a.d, 31 56 14.89.2010 14:.12.2010 III D II a.d, a,d, BM: 4 0 20,03,2010 10 HI. 201.0 III 0 II a.d. a.d. MR 4 7 30,07,2010 16,11.2010 111 0 111 0 pas. pern, GO 38 19.08.2010 19,12.2010 ΓΗ 0 II a.d. ft,ft. η. ft. : not delftaftiaad: ft.a.: not available nag. ; as g a t. las aaa.; positive
By the application ct the acidified sodium selenite gel in two patients it: canid be shown that the gel exhibits an effect according to the present invention and may tee used in the treatment of cervical dysplasia, in an efficient manner,
Example 4: Treatment of a squamous cell carcinoma of the
Cervix uteri in a iO-year-oici patient with acidified sodium selenite gel (prepared according to. Example 1}
Due to a pronounced dysplasia of the uterus (stage BAD XVy hi opti c according to CIN 3) patient 1G, born on 31 December 197 3, was subjected to a conization and a curettage of the cervix during her hospitaiiration period from 29 May 2008 to 02 dune 2000 at a general public hospital in Austria, Further: examinations;, including the histological examination of a tissue sample obtained from the patient, resulted in the diagnosis of an invasive squamous cell carcinoma of the Cervix uteri and of ft carcinoma in situ with stage: F’XGU IB 1, This result was confirmed in a Subsequent in-pa i. lent stay at the gynecological department of another Austrian hospital, CT, MEI and sonographic examinations resulted in the diagnosis of an obviously realign tumor with a site of 1G to 12 run located in the cranial region of the Cervix uteri, already spreading to the Isthmus uteri, but yet without lymphogenic metastatic spread. Not least because of the location of the residual tumor in the regier; of the is the: os uteri, these results led to a therapeutic recommendation for radical surgery according to berthelm FIVER II as any uterus-preserving surgery was not possible given the location of the tumor< Despite the enormous time pressure for making a decision, the patient obtained a second medical opinion and finally decided to undergo a potentially uterus-preserving therapy with the preparation according to the present invention. After a four-month period of therapy with the gel according to the present invention, a continuous gynecological, radiological and histological monitoring of the patient yielded a substantial reduction in tumor site as well as a remission of the inflammation. After two further months of therapy with the preparation according to the present invention the tumor had vanished and the histological smear yielded a remission of the inflammation to PAP lie.
Claims (6)
- SzabadaImi igénypontok »1. S sel en i. t - ta r t a imû veyyületet és cífcromsav, ecetsav, alma-sav, Ménsa-v,. kénsav, palbtrombay, sósav, gyümölcs-sávak,: vagy ezek keverékei közül választott gyögfázébéssééileg elfogadható savakat tartalmazó gyógyszerkészítmény PAP-score > PAP 111 és/vagy ClN-asoete > CIN i méhryak-segt elváltozások kezelésére történő alkalmazáshoz. 2V Készítmény az 1. igénypont szerinti alkalmazáshoz azzal jellemezve/ Begy töpikáíiSí mnkozális illetve intravagíoá-lis adagoláshoz került kikészítésre. '3. Készítmény az 1. vagy 2. igénypont szerinti a!; kalmazashoz azzal jeliemezve, hogy gélképzőt tartalmaz.
- 4. Készítmény az 1. ~ 3, igénypontok bármelyike szerinti alkalmazáshoz azzal jel lemez ve, hogy hidrogéXképzGt. tartalma z f kü i é n ő s én ee IX u l ó z -az á r ma z é ko ka t.
- 5. Készítmény ai 1 - 4. igénypontok bármelyike szerinti alkalmazáshoz azzal jellemezve, hegy karboximetilceilulóz, hidroKÍpropilcellulőz, metilce11 ülőx és hidrokidfeileexin-lőx közül kiválasztott gélképzőt, különösen: χ<^:·χ~ lulózt tartalmaz.
- 6. Készítmény a z 1. - 5. igénypontok bármelyike szerinti alkalmazáshoz azzal jellemezve, hogy gél formában Van és nagy diszpérzítáéö ézílicínm-dioxidot tartalmaz technológiai sztiszpenzié-hordozóként és/vagy adszotfeehskiht.
- 7. Készítmény az 1, - 6. igénypontok bármelyike szerinti alkalmazáshoz ázzál jellemmzvé, Bögy pl-értéke 7,:q alatti előnyösen 5,0 alatti, különösen 4,0 - 2,5 közötti.
- 8. Készítmény az 1, - 1. igénypontok bármelyike dl- halmazáéhoz ázzal jellemezve, hagy oldat, emirlzioí kenőcs vagy szivacs {tampon) formában van. ö, Kés sit snén y âK I> ~ I* igénypontok bármelyike szerinti alkalma zá shot azzal jel lemezve, hogy további segédanyagokat és/vagy további hatékony komponensekot tartalmaz, különösen puffer vegyûieteket, színezékekét stabilizáló anyagokat, hordozó anyagokat vagy ekék kombináclóit, .10, Kés2Ítmény at 1. - 9· igénypontok bármelyike szerinti alkalmazáshoz azzal jellemezve, hogy antibiotikumokat, an-tivirálís szereket, gombádlő szereket, fájdalomcsillapító szereket, gyuliáéáágáflo szereket, vagy ezek kombinációit tartalmazza, 11»készítmény az 1» - 10» igénypontok barmelyike szerinti al> ka ima zás hoz ászai jellemezve, hogy azt FAP-score PAP III és PAP 11ID méhnyak-gyulladások kezelésére használjuk, 12»Késkitmény az 1, - 11, igénypontok bármelyike szerinti alkalmazáshoz azzal jellemezve, hogy méhnyak-karcinömák kezelésére használjuk.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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ATA201/2011A AT511159A1 (de) | 2011-02-16 | 2011-02-16 | Pharmazeutische zusammensetzungen enthaltend selenit- oder selenathältige verbindungen |
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HUE029811T2 true HUE029811T2 (hu) | 2017-03-28 |
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HUE12707218A HUE029811T2 (hu) | 2011-02-16 | 2012-02-16 | Szelenitet vagy szelenit-tartalmú vegyületet tartalmazó gyógyszerkészítmény méhnyak-diszpláziák vagy -karcinómák kezelésére |
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US (3) | US10201566B2 (hu) |
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Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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DE102012222956A1 (de) * | 2012-12-12 | 2014-06-12 | Beiersdorf Ag | Kosmetische Zubereitungen mit Fließgrenze |
EP3616693A1 (en) * | 2018-08-28 | 2020-03-04 | Selo Medical GmbH | Therapy of high-risk human papillomavirus infections |
US20220288109A1 (en) * | 2019-08-30 | 2022-09-15 | Musc Foundation For Research Development | Sphingolipid-based selenium compounds, methods for their preparation, and pharmaceutical uses thereof, including as antitumor agents |
EP3875083A1 (en) * | 2020-03-03 | 2021-09-08 | Selo Medical GmbH | Composition for use in a treatment of cervical cell abnormalities comprising selenite compound and acid |
US20230233498A1 (en) * | 2020-06-26 | 2023-07-27 | Prothione, Llc | Compositions and methods for the treatment of covid-19 |
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CA1112164A (en) | 1977-08-02 | 1981-11-10 | Joseph R. Levitt | Therapeutic selenium compositions and the use thereof |
US4512977A (en) | 1979-10-18 | 1985-04-23 | Lundy Research Laboratories, Inc. | Therapeutic selenium compositions and the use thereof |
IT1161213B (it) | 1983-03-08 | 1987-03-18 | Fcn Srl | Composizioni farmaceutiche ad attivita' antineoplastica |
US4762726A (en) | 1983-12-30 | 1988-08-09 | Kraft, Inc. | Shelf stable acid food dressings containing fibrous protein complexes |
US4668515A (en) | 1984-03-06 | 1987-05-26 | Paul Bankit | Method and compositions for sodium selenite administration |
US5389677B1 (en) | 1986-12-23 | 1997-07-15 | Tristrata Inc | Method of treating wrinkles using glycalic acid |
US5153230A (en) | 1989-10-06 | 1992-10-06 | Perfective Cosmetics, Inc. | Topical skin cream composition |
US5182104A (en) | 1991-07-16 | 1993-01-26 | Stanley Marcus | Topical virucidal composition for treatment of mucocutaneous tissue |
CZ218394A3 (en) | 1992-03-11 | 1995-01-18 | Procter & Gamble | Plantain drinking mixtures containing granulated base |
US5425944A (en) | 1992-10-27 | 1995-06-20 | Harich; Jakob | Antimicrobial grapefruit extract |
US5536497A (en) | 1992-12-21 | 1996-07-16 | The Research Foundation Of State University Of New York | Fimbrial polypeptides useful in the prevention of periodontitis |
DE4320694C2 (de) | 1993-06-22 | 1999-11-11 | Biosyn Arzneimittel Gmbh | Vewendung von Selenverbindungen zur äußeren Anwendung bei Warzen |
US5484612A (en) | 1993-09-22 | 1996-01-16 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating a mammal having a solid tumor susceptible to treatment with cisplatin |
DE4335441A1 (de) | 1993-10-18 | 1995-04-20 | Hans Dipl Chem Heide | Mittel zur Gesundheitsvorsorge im Herz- Kreislaufsystem beim Menschen |
US5512200A (en) | 1994-04-18 | 1996-04-30 | Thomas G. Bongard | Low pH Acidic Compositions |
DE4413839C1 (de) | 1994-04-21 | 1995-10-19 | Fritz Koch Pharma Gmbh Dr Med | Kombinationspräparat |
DE69629874T2 (de) | 1995-06-07 | 2004-07-08 | Life Science Labs, Inc., Minneapolis | Selen enthaltende Zusammensetzung zur Reduzierung der Krebshäufigkeit und zur Verlängerung des Lebensalters |
GB2323030A (en) | 1997-03-12 | 1998-09-16 | Essential Nutrition Ltd | Dietary supplements for immunocompromised patients |
US5999844A (en) * | 1997-04-23 | 1999-12-07 | Accumed International, Inc. | Method and apparatus for imaging and sampling diseased tissue using autofluorescence |
US6069152A (en) | 1997-10-07 | 2000-05-30 | Eli Lilly And Company | 5-HT4 agonists and antagonists |
GB9722361D0 (en) | 1997-10-24 | 1997-12-17 | Pharma Nord Uk Ltd | Pharmaceutical formulation for treating liver disorders |
IT1297080B1 (it) | 1997-11-26 | 1999-08-03 | Andrea Carnevali | Composizione per il trattamento di ustioni, eritemi solari, abrasioni, piaghe e irritazioni cutanee |
US6228347B1 (en) | 1997-12-01 | 2001-05-08 | Thione International, Inc. | Antioxidant gel for gingival conditions |
FR2779720B1 (fr) | 1998-06-12 | 2002-08-16 | Galderma Rech Dermatologique | Nouveaux composes diarylselenures et leur utilisation en medecine humaine ou veterinaire ainsi qu'en cosmetologie |
US6120758A (en) | 1998-07-16 | 2000-09-19 | Shaklee Corporation | Preservative system for topically applied products |
FR2782642B1 (fr) | 1998-08-31 | 2001-12-07 | Xavier Forceville | Utilisation du selenium pour le traitement de patients atteints d'un syndrome de reponse inflammatoire systemique (sirs), et composition pour la mise en oeuvre du traitement |
US6114348A (en) | 1999-03-10 | 2000-09-05 | Weber; Paul J. | Method of treating warts using tazarotene |
AU2001259927B2 (en) | 2000-05-10 | 2005-02-24 | Okopharm Forschungs-Und Entwicklungs-Gmbh | Method for reducing the surface of silicon dioxide |
AT412758B (de) | 2000-06-05 | 2005-07-25 | Vis Vitalis Lizenz & Handels | Verwendung einer selenithältigen lösung zur behandlung viraler erkrankungen |
AT412448B (de) | 2001-02-13 | 2005-03-25 | Vis Vitalis Lizenz & Handels | Verwendung von selenhältigen präparaten |
AT412703B (de) * | 2001-12-04 | 2005-06-27 | Vis Vitalis Lizenz & Handels | Verwendung von selenithältigen präparaten zur topischen oder bukkalen anwendung |
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