IT9021735A1 - CALCITONIN PHARMACEUTICAL COMPOSITIONS - Google Patents
CALCITONIN PHARMACEUTICAL COMPOSITIONS Download PDFInfo
- Publication number
- IT9021735A1 IT9021735A1 IT021735A IT2173590A IT9021735A1 IT 9021735 A1 IT9021735 A1 IT 9021735A1 IT 021735 A IT021735 A IT 021735A IT 2173590 A IT2173590 A IT 2173590A IT 9021735 A1 IT9021735 A1 IT 9021735A1
- Authority
- IT
- Italy
- Prior art keywords
- pharmaceutical compositions
- calcitonin
- monobasic
- citrate
- solution
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 102000055006 Calcitonin Human genes 0.000 title claims description 10
- 108060001064 Calcitonin Proteins 0.000 title claims description 10
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 title claims description 10
- 229960004015 calcitonin Drugs 0.000 title claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 8
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 5
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 5
- 229960003194 meglumine Drugs 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 229940069328 povidone Drugs 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- 229960000281 trometamol Drugs 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 claims description 3
- 241000972773 Aulopiformes Species 0.000 claims description 3
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 3
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 3
- 235000019515 salmon Nutrition 0.000 claims description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims 1
- 108010068072 salmon calcitonin Proteins 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Description
Descrizione dell'invenzione industriale dal titolo: Description of the industrial invention entitled:
"Composizioni farmaceutiche a base di calcitonine" "Pharmaceutical compositions based on calcitonins"
CAMPO DELL’INVENZIONE FIELD OF THE INVENTION
L’invenzione riguarda composizioni farmaceutiche adatte alla somministrazione di calcitonina per via nasale. The invention relates to pharmaceutical compositions suitable for the administration of calcitonin via the nose.
STATO DELLA TECNICA STATE OF THE TECHNIQUE
Le calcitonine costituiscono una classe di polipeptidi a lunga catena, che sono state isolate da organi di varie specie animali e che sono ottenibili anche per via sintetica. Esse sono correntemente impiegate nel trattamento di varie malattìe: per esempio le calcitonine di salmone e di anguilla si sono dimostrate particolarmente efficaci nel trattamento della malattia di Paget, dell'ipercalcemia e dell'osteoporosi. La somministrazione delle calcitonine è stata per lungo tempo effettuata soprattutto per via iniettiva. Questo metodo però presenta vari inconvenienti per trattamenti prolungati. Si sono quindi tentati altri metodi di somministrazione e fra questi si è dimostrata particolarmente efficace e conveniente la somministrazione per via nasale; sono state quindi studiate varie formulazioni comprendenti calcitonine adatte per essere assorbite per questa via. Calcitonins constitute a class of long-chain polypeptides, which have been isolated from organs of various animal species and which are also obtainable synthetically. They are currently used in the treatment of various diseases: for example, salmon and eel calcitonins have proved particularly effective in the treatment of Paget's disease, hypercalcemia and osteoporosis. The administration of calcitonins was for a long time mainly carried out by injection. However, this method has various drawbacks for prolonged treatments. Other methods of administration have therefore been tried and among these the nasal administration has proved to be particularly effective and convenient; various formulations including calcitonins suitable for being absorbed by this route have therefore been studied.
SOMMARIO DELL'INVENZIONE SUMMARY OF THE INVENTION
L'invenzione riguarda composizioni farmaceutiche a base di calcitonine in soluzione acquosa, particolarmente adatte per la somministrazione per via nasale. Le composizioni comprendono: una calcitonine, esteri alchilici dell'acido p-idrossibenzoico, trometamina citrato monobasico, meglumina citrato monobasico, povidone ed acido citrico in determinate proporzioni. The invention relates to pharmaceutical compositions based on calcitonins in aqueous solution, particularly suitable for administration by the nasal route. The compositions comprise: a calcitonin, p-hydroxybenzoic acid alkyl esters, monobasic tromethamine citrate, monobasic meglumine citrate, povidone and citric acid in certain proportions.
DESCRIZIONE DETTAGLIATA DELL'INVENZIONE DETAILED DESCRIPTION OF THE INVENTION
Le composizioni farmaceutiche dell'invenzione sono soluzioni acquose, che comprendono, per millilitro di soluzione: The pharmaceutical compositions of the invention are aqueous solutions, which comprise, per milliliter of solution:
- una calcitonine, preferibilmente di salmone, in quantità compresa fra 300 e 3000 U.I., preferibilmente tra 400 e 800 U.I. ; - a calcitonin, preferably of salmon, in a quantity comprised between 300 and 3000 IU, preferably between 400 and 800 IU. ;
- esteri alchilici dell'acido p-idrossibenzoico: preferiti sono il p-idrossibenzoato di metile, in quantità compresa tra 0,1 e 10 mg, preferibilmente tra 0,5 e 2,0 mg, e il pidrossibenzoato di propile, in quantità compresa tra 0,01 e 1 mg, preferibilmente tra 0,05 e 0,2 mg; preferibilmente, entrambi gli esteri suddetti sono presenti nella formulazione; - alkyl esters of p-hydroxybenzoic acid: preferred are methyl p-hydroxybenzoate, in a quantity comprised between 0.1 and 10 mg, preferably between 0.5 and 2.0 mg, and propyl phydroxybenzoate, in an quantity comprised between 0.01 and 1 mg, preferably between 0.05 and 0.2 mg; preferably, both of the aforesaid esters are present in the formulation;
- trometamina citrato monobasico, in quantità compresa tra 1 e 20 mg, preferibilmente tra 4 e 6 mg; - monobasic tromethamine citrate, in a quantity ranging from 1 to 20 mg, preferably from 4 to 6 mg;
- meglumina citrato monobasico, in quantità compresa tra 1 e 20 mg, preferibilmente tra 5 e 10 mg; - monobasic meglumine citrate, in a quantity ranging from 1 to 20 mg, preferably from 5 to 10 mg;
- povidone, in quantità compresa tra 1 e 50 mg, preferibilmente tra 5 e 20 mg; - povidone, in a quantity ranging from 1 to 50 mg, preferably from 5 to 20 mg;
- acido citrico, in quantità sufficiente a portare il pH della soluzione tra 3.5 e 4,5, preferibilmente tra 3.8 e 4. - citric acid, in a quantity sufficient to bring the pH of the solution between 3.5 and 4.5, preferably between 3.8 and 4.
Particolarmente efficace si è dimostrata una formulazione comprendente, per 1 millilitro di soluzione acquosa: Particularly effective has proved to be a formulation comprising, for 1 milliliter of aqueous solution:
Le composizioni dell'invenzione possono essere somministrate o in gocce o sotto forma di spray, con mezzi noti. The compositions of the invention can be administered either in drops or in the form of a spray, by known means.
Le composizioni dell'invenzione sono molto stabili: la calcitonina si degrada in misura trascurabile, se mantenuta a temperatura non superiore a 22°C in recipienti di vetro per 18 mesi. Anche la resistenza all'attacco di microbi è molto elevata, come risulta aggiungendo alle soluzioni secondo l'invenzione batteri vari: dopo poco tempo si nota la sparizione pressoché completa di detti batteri. The compositions of the invention are very stable: calcitonin degrades to a negligible extent, if kept at a temperature not exceeding 22 ° C in glass containers for 18 months. The resistance to attack by microbes is also very high, as can be seen by adding various bacteria to the solutions according to the invention: after a short time, the almost complete disappearance of said bacteria is noted.
Prove cliniche hanno dimostrato che le composizioni dell’invenzione sono ben tollerate dall'organismo dando solo disturbi di lieve entità anche per trattamenti prolungati. Prove di biodisponibilità relativa dimostrano che l’assorbimento nel sangue di calcitonina riscontrato somministrando per via nasale le composizioni dell'invenzione è paragonabile a quello riscontrato somministrando per via intramuscolare lo stesso principio attivo contenuto in formulazioni note. Clinical tests have shown that the compositions of the invention are well tolerated by the body, giving only minor disturbances even for prolonged treatments. Relative bioavailability tests show that the absorption into the blood of calcitonin found by administering the compositions of the invention via the nose is comparable to that found by administering the same active ingredient contained in known formulations intramuscularly.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02173590A IT1243742B (en) | 1990-10-12 | 1990-10-12 | Calcitonin-based pharmaceutical compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02173590A IT1243742B (en) | 1990-10-12 | 1990-10-12 | Calcitonin-based pharmaceutical compositions |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IT9021735A0 IT9021735A0 (en) | 1990-10-12 |
| IT9021735A1 true IT9021735A1 (en) | 1992-04-12 |
| IT1243742B IT1243742B (en) | 1994-06-21 |
Family
ID=11186136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT02173590A IT1243742B (en) | 1990-10-12 | 1990-10-12 | Calcitonin-based pharmaceutical compositions |
Country Status (1)
| Country | Link |
|---|---|
| IT (1) | IT1243742B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20021684A1 (en) * | 2002-07-29 | 2004-01-29 | Therapicon Srl | PHARMACEUTICAL COMPOSITION OF NASAL PEPTIDE |
-
1990
- 1990-10-12 IT IT02173590A patent/IT1243742B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| IT1243742B (en) | 1994-06-21 |
| IT9021735A0 (en) | 1990-10-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 0001 | Granted | ||
| TA | Fee payment date (situation as of event date), data collected since 19931001 |
Effective date: 19971030 |