Protein formulation comprising growth hormone

Details Protein formulation comprising growth hormone Protein formulation comprising growth hormone

1993-12-20

1996-10-22

Sayala, Chhaya D.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 21, 530399, A61K 3827

Patent

active

055676774

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to formulation of growth hormone or any functional analogue thereof, especially human growth hormone (hGH) in solutions, which comprise citrate in an concentration of about 2 to 50 mM as buffer substance and especially sodium citrate in an concentration of about 2 to 20 mM. This buffer is used for improving stability.
Growth hormone can be both human and animal such as human growth hormone (hGH), bovine growth hormone (bGH) and porcine growth hormone (pGH).
hGH is a protein Consisting of a single chain of 191 amino acids. The molecule is cross-linked by two disulphide bridges and the monomeric form has a molecular weight of 22 kDa. However, pituitary human growth hormone is not homogeneous. For example, a smaller 20 kDa hGH variant produced from the same gene is also known. The "basic hGH" variant (hGH-V) expressed by the placenta during pregnancy is another analogue which is a product of a separate gene. Like the 22 kDa hGH it consists of 191 amino acids but in various positions throughout the molecule 13 of them are different. See e.g. Bewley T. A. et al; Adv Enzymol; 42; 73-166; 1975 and Frankenne F. et al; J Ciin. Endocrin and Metabol; 66; 1171-80; 1988.
Recombinant hGH (22 kDa) has been commercially available for several years. It is preferred over the pituitary derived products because the product prepared from human tissue might contain infectious agents Such as that for the Creutzfeld-Jacob's disease. Two types of therapeutically useful recombinant hGH preparations are present on the market: the authentic one, e.g. Genotropin.RTM., Kabi Pharmacia AB, and an analogue with an additional methionine residue at the N-terminal end, e.g. Somatonorm.RTM..
hGH is used to stimulate linear growth in patients with hypo pituitary dwarfism or Turner's syndrome but other indications have also been suggested.
The stability of proteins in aqueous formulations is generally a problem in pharmaceutical industry.
It has often been solved by drying of the protein in different drying processes, such as freeze-drying. The protein has thereafter been distributed and stored in dried form. The patient necessarily has to reconstitute the dried protein in a solvent before use, which of course is a disadvantage and is an inconvenience for the patient.
By new devices for administrations, e.g. Kabipen.RTM. which is described in U.S. Pat. No. 4,968,299, Kabi Pharmacia AB, the patient has got a device which is rather simple to handle. The device comprises a two-chamber ampoule Genomix.RTM. containing hGH as a lyophilised powder in one of the compartments and a reconstitution diluent in the other. The patient reconstitutes the product before use. The lyophilised product can be stored for up to 24-months. The reconstituted product is then stable for 3 weeks when stored at 2.degree.-8.degree. C.
The freeze-drying process is a costly and time consuming process step, and it would be of great advantage if this step could be avoided, when preparing a commercial product of a protein.
For a patient, who needs daily injections of a growth hormone e.g. hGH, and especially when the patient is a child, it is of importance that the product is easy to handle, to dose and inject. The reconstitution of freeze-dried hGH demands prudence and carefulness and should preferably be avoided, but is the only method available today.
It would facilitate the use of growth hormone and especially hGH, if the protein could be produced and distributed as a solution to the patient, who could inject the medicament directly without reconstitution.
Different solutions to this problem have been disclosed, but until now no product has appeared on the market.
In WO 89/09614, Genentech, a stabilised formulation of hGH comprising glycine, mannitol and a buffer is disclosed and in a preferred embodiment a non-ionic surfactant such as polysorbate 80 is added. Sodium-phosphate is suggested as buffer substance. The formulation has an increased stability in a lyophilised formulation and upon reconstitution.
Another possibility of administering gro

REFERENCES:
patent: 4783441 (1988-11-01), Thurow
patent: 4816568 (1989-03-01), Hamilton, Jr. et al.
patent: 4917685 (1990-04-01), Viswanathan et al.
patent: 4963529 (1990-10-01), Fujioka et al.
patent: 5008244 (1991-04-01), Miller et al.
patent: 5021241 (1991-06-01), Yamahira et al.
patent: 5096885 (1992-03-01), Pearlman et al.
The U.S. Pharmacopeia, 21st Edition, 1985, pp. 1491-1493.
Skottner et al., Endocrinology, vol 124(5), 1989, pp. 2519-2526.
Chemical Abstract, vol. 113 (1990) pp. 374, Item 12165x.
The Merch Index, Eleventh Edition, 1989, pp. 1373-1374.

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