ITMI961921A1 - USE OF PROTEINS AS ANTI-DIABETIC AGENTS - Google Patents
USE OF PROTEINS AS ANTI-DIABETIC AGENTS Download PDFInfo
- Publication number
- ITMI961921A1 ITMI961921A1 ITMI961921A ITMI961921A1 IT MI961921 A1 ITMI961921 A1 IT MI961921A1 IT MI961921 A ITMI961921 A IT MI961921A IT MI961921 A1 ITMI961921 A1 IT MI961921A1
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- IT
- Italy
- Prior art keywords
- proteins
- protein
- diabetes
- diabetic agents
- administration
- Prior art date
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- 102000004169 proteins and genes Human genes 0.000 title claims description 17
- 108090000623 proteins and genes Proteins 0.000 title claims description 17
- 239000003472 antidiabetic agent Substances 0.000 title description 3
- 229940125708 antidiabetic agent Drugs 0.000 title description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 102000006303 Chaperonin 60 Human genes 0.000 description 5
- 108010058432 Chaperonin 60 Proteins 0.000 description 5
- 230000007170 pathology Effects 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 230000003178 anti-diabetic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 108050001186 Chaperonin Cpn60 Proteins 0.000 description 2
- 102000052603 Chaperonins Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
Descrizione dell'invenzione industriale avente per titolo: "USO DI PROTEINE COME AGENTI ANTIDIABETICI" Description of the industrial invention entitled: "USE OF PROTEINS AS ANTIDIABETIC AGENTS"
La presente invenzione ha per oggetto l'uso di proteine estraibili da organi animali, per la preparazione di medicamenti ad attività antidiabetica. The present invention relates to the use of proteins extractable from animal organs, for the preparation of medicaments with antidiabetic activity.
E' stato dimostrato che la somministrazione di adiuvante di Freund completo è in grado di indurre nel ratto una artrite sperimentale con molte somiglianze alla artrite reumatoide. La somministrazione di adiuvante al coniglio non provoca la patologia artritica, bensì induce aterosclerosi. Gli studi condotti hanno evidenziato che in entrambe le lesioni si manifesta la presenza di immunoreattività per un fattore endogeno, identificato nella Heat Shock Protein 60 (HSP60). Studi successivi hanno confermato queste osservazioni e hanno dimostrato che la somministrazione dell’adiuvante completo di Freund può essere sostituita con la somministrazione di HSP60, risultando nelle stesse patologie . E' stato successivamente dimostrato nel ratto che il pretrattamento con l'adiuvante, la HSP60 o suoi frammenti è in grado di prevenire l'insorgere dell'artrite, con un meccanismo non ancora chiarito, al contrario la somministrazione successiva all 'adiuvante peggiora la progressione della malattia. The administration of complete Freund's adjuvant has been shown to induce experimental arthritis in rats with many similarities to rheumatoid arthritis. The administration of adjuvant to the rabbit does not cause arthritic disease, but rather induces atherosclerosis. The studies carried out have shown that in both lesions the presence of immunoreactivity for an endogenous factor, identified in the Heat Shock Protein 60 (HSP60) is manifested. Subsequent studies have confirmed these observations and have shown that the administration of Freund's complete adjuvant can be replaced with the administration of HSP60, resulting in the same pathologies. It was subsequently demonstrated in rats that pretreatment with the adjuvant, HSP60 or its fragments is able to prevent the onset of arthritis, with a mechanism not yet elucidated, on the contrary, subsequent administration to the adjuvant worsens the progression. of the disease.
Più recentemente, è stato osservato che il pretrattamento con adiuvante era in grado di prevenire anche altre patologie sperimentali che possono essere definite, in modo generale, su base autoimmune, come il diabete o la encefalomielite allergica sperimentale (EAE). Infine, è stato scoperto che HSP60 mostra analogie strutturali con un elevato numero di autoantigeni, lasciando prevedere che il suo coinvolgimento in patologie sia molto più ampio di quanto fino ad ora osservato. More recently, it has been observed that pretreatment with adjuvant was also able to prevent other experimental diseases that can be defined, in a general way, on an autoimmune basis, such as diabetes or experimental allergic encephalomyelitis (EAE). Finally, it has been found that HSP60 shows structural similarities with a high number of autoantigens, suggesting that its involvement in pathologies is much wider than what has been observed up to now.
In WO 92/10197 sono state descritte frazioni proteiche estraibili con acido perclorico da organi di mammiferi, e il loro uso come agenti antitumorali. All'interno di queste frazioni potevano essere riconosciute tre componenti principali, di peso molecolare di 50, 14 e 10 KDa su gel elettroforesi. L'estratto purificato contenente queste tre componenti sarà di seguito definito con la sigla UK 101. La sequenza della componente proteica a 14 KDa, che è la principale, se non l'unica, responsabile delle attività descritte, è riportata in Tabella 1 e in 96/02567 ed è risultata correiabile a quella descritta da altri autori (Levy-Favatier, Eur. Biochem. 1903, 212 (3) 665-73) che hanno ipotizzato l'appartenenza delle nuove sequenze identificate alla famiglia delle proteine note come chaperonine, a cui appartengono le stesse HSP. In WO 92/10197, protein fractions extractable with perchloric acid from mammalian organs, and their use as anticancer agents have been described. Within these fractions, three main components could be recognized, with molecular weights of 50, 14 and 10 KDa on gel electrophoresis. The purified extract containing these three components will be defined below with the initials UK 101. The sequence of the protein component at 14 KDa, which is the main, if not the only one, responsible for the activities described, is shown in Table 1 and in 96/02567 and was found to be correctable to that described by other authors (Levy-Favatier, Eur. Biochem. 1903, 212 (3) 665-73) who hypothesized that the new sequences identified belong to the family of proteins known as chaperonins, to which the HSPs themselves belong.
Le proteine descritte in WO 92/10197 e quelle WO 96/02567 (indicate di seguito con la sigla UK 114) presentano comunque proprietà mai riscontrate per le chaperonine o in proteine analoghe. Si è trovato in particolare che tali proteine possono essere utilizzate per la prevenzione e il trattamento del diabete. The proteins described in WO 92/10197 and those WO 96/02567 (indicated hereafter with the initials UK 114) show however properties never found for chaperonins or in analogous proteins. In particular, it has been found that such proteins can be used for the prevention and treatment of diabetes.
L'invenzione riguarda preferibilmente l'uso della proteina UK 114 purificata per la preparazione di medicamenti antidiabetici. The invention preferably relates to the use of purified UK protein 114 for the preparation of antidiabetic medicaments.
Inoltre l'invenzione comprende anche l'uso di proteine presentanti un grado di omologia rispetto a UK 114 di almeno l'80%, preferibilmente di almeno il 90%. Furthermore, the invention also includes the use of proteins having a degree of homology with respect to UK 114 of at least 80%, preferably at least 90%.
L’attività delle proteine UK 101 e UK 114 è stata messa in evidenza utilizzando un modello classico di diabete, rappresentato dal ratto BB che sviluppa spontaneamente diabete attorno al 45° giorno di vita. Gli animali sono stati trattati al 30° giorno di vita con UK101 o UK114 e si è seguito lo svilupparsi della patologia in confronto ad animali controllo non trattati con le due sostanze. Si è osservato che il pretrattamento riduceva l'incidenza e la gravità della patologia nel modello sperimentale. Alcuni pazienti affetti da tumori a diversa sede e portatori anche di patologia diabetica sono stati trattati con UK101 nel corso del trattamento compassionevole con la sostanza. In tutti i pazienti trattati, indipendentemente dall'effetto sulla patologia tumorale, si è osservata una remissione della patologia diabetica che giungeva fino all'abbandono della terapia insulinica. The activity of the UK 101 and UK 114 proteins was highlighted using a classic model of diabetes, represented by the BB rat that spontaneously develops diabetes around the 45th day of life. The animals were treated at day 30 with UK101 or UK114 and the development of the disease was followed in comparison to control animals not treated with the two substances. Pretreatment was found to reduce the incidence and severity of the disease in the experimental model. Some patients with multi-site cancers and also carriers of diabetic disease have been treated with UK101 during compassionate treatment with the substance. In all treated patients, regardless of the effect on the tumor pathology, a remission of the diabetic pathology was observed that went up to the abandonment of insulin therapy.
Si ritiene pertanto che UK101 e UK114 siano in grado di modificare il decorso o prevenire il diabete. It is therefore believed that UK101 and UK114 are capable of modifying the course or preventing diabetes.
L'attività antidiabetica è stata infatti confermata, sia pure in un numero per ora limitato di casi, anche in vivo su pazienti affetti da diabete . The antidiabetic activity has in fact been confirmed, albeit in a limited number of cases so far, also in vivo in patients with diabetes.
Le proteine dell'invenzione possono essere somministrate ricorrendo ad opportune formulazioni, per lo più iniettabili. The proteins of the invention can be administered using suitable formulations, mostly injectable.
Le modalità di somministrazione (dosi, frequenza di somministrazione, ecc.) saranno determinate caso per caso, a seconda di diversi fattori quali condizioni del paziente, stadio della malattia, ma è comunque da attendersi un intervallo di dosaggio giornaliero conpreso tra 1 e 100 mg. The methods of administration (doses, frequency of administration, etc.) will be determined on a case-by-case basis, depending on various factors such as the patient's condition, stage of the disease, but a daily dosage interval between 1 and 100 mg is to be expected. .
Claims (4)
Priority Applications (25)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI961921 IT1284555B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
IL12902497A IL129024A0 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agent against autoimmune diseases |
DK97910295T DK0928197T3 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents for autoimmune diseases |
EP97910295A EP0928197B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
BR9711499A BR9711499A (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
CA002266346A CA2266346A1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
CZ1999915A CZ293926B6 (en) | 1996-09-18 | 1997-09-17 | Pharmaceutical composition |
US09/269,019 US6468536B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as anti-diabetes agents |
CNB971980128A CN1151838C (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
ARP970104244A AR009952A1 (en) | 1996-09-18 | 1997-09-17 | USE OF PROTEINS AS AGENTS AGAINST AUTOIMMUNE DISEASES. |
PT97910295T PT928197E (en) | 1996-09-18 | 1997-09-17 | USE OF PROTEINS AS AGENTS AGAINST DISEASES OF AUTOIMUNITY NATURE |
NZ334714A NZ334714A (en) | 1996-09-18 | 1997-09-17 | Liver proteins as agents against autoimmune diseases |
TR1999/00596T TR199900596T2 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases. |
PCT/EP1997/005079 WO1998011909A1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
AT97910295T ATE233569T1 (en) | 1996-09-18 | 1997-09-17 | USE OF PROTEINS AS AN AGENT AGAINST AUTOIMMUNE DISEASES |
SI9730494T SI0928197T1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
RU99107658/14A RU2196606C2 (en) | 1996-09-18 | 1997-09-17 | Application of proteins as agents against autoimmune diseases |
JP10514285A JP2001501925A (en) | 1996-09-18 | 1997-09-17 | Use of proteins as substances for autoimmune diseases |
AU47747/97A AU723669B2 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
DE69719525T DE69719525T2 (en) | 1996-09-18 | 1997-09-17 | USE OF PROTEINS AS A MEDICINE AGAINST AUTOIMMUNE DISEASES |
ES97910295T ES2192669T3 (en) | 1996-09-18 | 1997-09-17 | USE OF PROTEINS AS AGENTS AGAINST AUTOIMMUNE DISEASES. |
KR1019997002267A KR20000036207A (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
NO991175A NO991175D0 (en) | 1996-09-18 | 1999-03-10 | Use of proteins as agents for autoimmune diseases |
PL97332282A PL188746B1 (en) | 1996-09-18 | 1999-03-17 | Application of proteins as factors against autoimmunological diseases |
US10/232,712 US20030108558A1 (en) | 1996-09-18 | 2002-09-03 | Use of proteins as agents against autoimmune diseases |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI961921 IT1284555B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
Publications (2)
Publication Number | Publication Date |
---|---|
ITMI961921A1 true ITMI961921A1 (en) | 1998-03-18 |
IT1284555B1 IT1284555B1 (en) | 1998-05-21 |
Family
ID=11374900
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ITMI961921 IT1284555B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
Country Status (1)
Country | Link |
---|---|
IT (1) | IT1284555B1 (en) |
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1996
- 1996-09-18 IT ITMI961921 patent/IT1284555B1/en active IP Right Grant
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Publication number | Publication date |
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IT1284555B1 (en) | 1998-05-21 |
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