| Sustained release of microcrystalline peptide suspensions -> Monitor Keywords |
|
|
 
Sustained release of microcrystalline peptide suspensionsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, CyclopeptidesSustained release of microcrystalline peptide suspensions description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060229238, Sustained release of microcrystalline peptide suspensions. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 10/080,130, filed Feb. 19, 2002, which claims priority to U.S. Provisional Application No. 60/317,616, filed Sep. 6, 2001, the entire disclosure of each of which is incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] There is frequently a need to deliver biologically active peptides to animals and humans in formulations providing a sustained release of the active principle. Such formulations may be provided by incorporating the active principle in biodegradable and biocompatible polymers in the form of microcapsules, microgranules or implantable rods, or alternatively using mechanical devices such as micropumps or non-biodegradable containers. If the peptide is highly soluble in aqueous media, it can be formulated as a complex with non-degradable polymers such as cellulose derivatives, or mixed with polymer solutions, which form a gel upon parenteral injection, from which the active peptide is slowly released. [0003] All the above-mentioned formulations have drawbacks and limitations, such as the large volume of suspending fluids or the need to remove the non-degradable device. In the case of gel forming peptides, there is frequently a problem of bioavailability, which interferes with the desired sustained action of the active principle. [0004] Some of the problems due to physico-chemical aspects of peptides have been described in an article by R. Deghenghi "Antarelix" in Treatment with GNRH Analogs: Controversies and Perspectives", edited by M. Filicori and C. Flamigni, The Parthenon Publishing Group, New York and London 1996, pages 89-91. Additional problems were illustrated by J. Rivier "GNRH analogues towards the next millennium" in GNRH Analogues, edited by B. Lunenfeld, The Parthenon Publishing Group, New York and London 1999, pages 31-45 and by other workers such as M. F. Powell et al. "Parenteral Peptide Formulations: Chemical and Physical Properties of Native LHRH and Hydrophobic Analogues in Aqueous Solution" in Pharmaceutical Research, Vol. 8, 1258-1263 (1991). [0005] Accordingly, there is a need for new formulations and methods of administration that avoid these problems, and this need is addressed by the present invention. SUMMARY OF THE INVENTION [0006] The present invention relates to a fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic and a counter-ion of a strong proton donor in water. The peptide or peptidomimetic and counter-ion are present in amounts and at a molar ratio sufficient to form the suspension of the peptide or peptidomimetic upon mixing without formation of a gel. [0007] In one embodiment, the counter-ion is trifluoromethanesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, or sulfuric acid. Generally, the counter-ion is a strong acid and the peptide is a GnRH analogue. The GnRH analogue is preferably a GnRH antagonist. [0008] In another embodiment, the GnRH antagonist is Ac-D-Nal-D-Cpa-D-Pal-Ser-Tyr-D-Hci-Leu-Ilys-Pro-D-Ala-NH.sub.2. In yet another embodiment, the GnRH antagonist is Azaline B, Abarelix, Antide, Ganirelix, Cetrorelix, or FE200486 and is in the form of an alkylsulfonate, arylsulfonate, trifluoroacetate or sulfate salt. [0009] The peptide may also be a somatostatin analogue. The somatostatin analogue may be, for example, Vapreotide, Octreotide, Lanreotide or SOM 230. [0010] Generally, the peptide or peptidomimetic forms a salt with the counter-ion, and the salt is suspended in the aqueous medium at a concentration of equal to or higher than 25 mg/mL. The aqueous suspension usually contains an isotonic agent, such as mannitol. [0011] Typically, the suspension also includes a pharmaceutically acceptable excipient. The amount of peptide or peptidomimetic generally ranges from about 0.1 to 5 mg per kg body weight of a mammal or human to which the suspension is to be administered. The peptide is preferably at least partially in the form of microcrystals having a particle size of from about 1 .mu.m to 150 .mu.m. [0012] The present invention also relates to a lyophilized composition that includes a dried suspension. In addition, the present invention relates to a method of making the lyophilized composition by associating the peptide or peptidomimetic with a counter-ion of a strong proton donor in an amount and at a molar ratio that are sufficient to provide the suspension without formation of a gel, and lyophilizing the suspension to obtain the composition. [0013] The present invention further relates to a method of preparing a fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic that includes adding water or a buffer solution to the lyophilized composition with mixing to obtain the suspension. [0014] A method of preparing a fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic is also encompassed by the present invention. The method includes associating the peptide or peptidomimetic with the counter-ion in an amount and at a molar ratio with the peptide that are sufficient to provide the fluid, milky microcrystalline aqueous suspension without formation of a gel; lyophilizing the suspension to form a lyophilized composition; and adding water or a buffer solution to the lyophilized composition with mixing to obtain the suspension. [0015] Furthermore, the present invention relates to a method of preparing a fluid, milky microcrystalline aqueous suspension of a peptide or peptidomimetic that includes associating the peptide or peptidomimetic with the counter-ion in an amount and at a molar ratio that are sufficient to provide the fluid, milky microcrystalline aqueous suspension without formation of a gel. [0016] The suspension is generally prepared to provide a sustained release formulation of the peptide or peptidomimetic such that, when administered to a subject, the peptide or peptidomimetic is released in vivo over a period of at least two weeks. Preferably, the counter-ion is a trifluoromethanesulfonic acid, benzenesulfonic acid, trifluoroacetic acid or sulfuric acid. Typically, the counter-ion is a strong acid and the peptide is a GnRH analogue. The GnRH analogue is, for example, a GnRH antagonist. The GnRH antagonist is preferably Ac-D-Nal-DCpa-D-Pal-Ser-Tyr-Hci-Leu-Ilys-Pro-D-Ala-NH.sub.2. The GnRH antagonist is typically Azaline B, Abarelix, Antide, Ganirelix, Cetrorelix, or FE200486 and is in the form of an alkylsulfonate, arylsulfonate, trifluoroacetate or sulfate salt. [0017] The peptide is typically a somatostatin analogue. Preferably, the somatostatin analogue is Vapreotide, Octreotide, Lanreotide, or SOM 230. The peptide or peptidomimetic usually forms a salt with the counter-ion, and the salt is suspended in the aqueous medium at a concentration of at least 25 mg/mL. [0018] In one embodiment, the aqueous suspension is injected parenterally into a mammal or human subject to obtain a sustained release of the peptide or peptidomimetic over at least one month. The amount of peptide or peptidomimetic in the suspension to be injected generally ranges from about 0.1 to 5 mg per kg body weight of the mammal or human subject. [0019] A sustained release formulation of a peptide or peptidomimetic prepared by the method of the present invention, when administered to a subject, generally releases the peptide or peptidomimetic in vivo over a period of at least two weeks. BRIEF DESCRIPTION OF THE DRAWINGS [0020] FIG. 1 is a graph which illustrates the pharmacodynamic effect (testosterone suppression) obtained by subcutaneous injection in rats of a suspension of Teverelix trifluoroacetate according to the invention; and Continue reading about Sustained release of microcrystalline peptide suspensions... Full patent description for Sustained release of microcrystalline peptide suspensions Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Sustained release of microcrystalline peptide suspensions patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Sustained release of microcrystalline peptide suspensions or other areas of interest. ### Previous Patent Application: Cyclic tetrapeptide compound and use thereof Next Patent Application: Treatment of gastrointestinal distress Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Sustained release of microcrystalline peptide suspensions patent info. IP-related news and info Results in 0.10878 seconds Other interesting Feshpatents.com categories: Medical: Surgery , Surgery(2) , Surgery(3) , Drug , Drug(2) , Prosthesis , Dentistry 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
