Somatotropin composition with improved syringeability

Details Somatotropin composition with improved syringeability Somatotropin composition with improved syringeability

2001-11-21

2004-05-11

Page, Thurman K. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Matrices

C424S484000, C424S485000, C424S422000

Reexamination Certificate

active

06733786

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a composition containing somatotropin having activity in vivo, and particularly, to a composition which can obtain the sustained release effect of the pharmaceutical to avoid the inconvenience of daily administration as well as have the suitable syringeability for being parenterally administered into animals to solve problems during injection, in which somatotropin is mixed with excipients.
DESCRIPTION OF THE PRIOR ART
Recently, somatotropin which can be produced in a large scale by using recombinant DNA technology according to development of genetic engineering has been commercially available for increasing the productivity of milk in cattle, and has been studied for improving feed efficiency and meat quality in swine.
Most of formulations developed hitherto for administering somatotropin having activity in vivo are simply the long acting types wherein a large amount of somatotropin is administered to avoid the inconvenience of daily administration. For example, U.S. Pat. No. 5,411,951 and U.S. Pat. No. 5,474,980 disclose sustained release formulations prepared by adding a gelling agent such as aluminum monostearate into vegetable oil; by gelling the oil by heating; and by mixing somatotropin or other drugs with it homogeneously, because drugs become phase-separated and precipitated in short time when only vegetable oil is used. These techniques have been already used to prepare the sustained release formulations of various drugs such as known antibiotics(U.S. Pat. No. 2,491,537, U.S. Pat. No. 2,507,193 and U.S. Pat. No. 3,016,330), pamoate salts of oxazepines(U.S. Pat. No. 3,676,557) or relaxin which is a kind of hormone(U.S. Pat. No. 2,964,448), adrenocorticotropic hormone(U.S. Pat. No. 3,869,549), luteinizing hormone releasing factor(U.S. Pat. No. 4,256,737), gonadotropin(U.S. Pat. No. 3,852,422) and insulin(U.S. Pat. No. 2,143,590, U.S. Pat. No. 2,174,862, U.S. Pat. No. 2,882,203, U.S. Pat. No. 2,920,014 and U.S. Pat. No. 3,102,077) and the like.
There are similar prior art techniques using oil simply for preparing sustained release formulations. For example, EP 211691 discloses that somatotropin is mixed with a mixture of wax and oil and EP 213851 discloses that the sustained release formulation is prepared by mixing somatotropin with a mixture of oil and commercially available glyceride release-modifying agent. Also, EP 314421 discloses that sustained release formulations of somatotropin are prepared by adding absorption controlling material(e.g., calcium stearate and dextran) to oil. But these are also the formulations wherein the active ingredients in the known injectable formulations containing oil used for other drugs have been substituted with somatotropin.
In addition, the sustained release techniques without using oil have been attempted. For example, in EP 193917, somatotropin was mixed with water-soluble carbohydrate polymer(e.g., starch, dextrin) to improve the sustained release effect. However, it has shorter duration of action than formulations mixed in oil, and it may do harm on stability of somatotropin due to its water-solubility.
Different techniques from the above-mentioned techniques have been attempted for lengthening duration of action of somatotropin formulations. U.S. Pat. No. 4,861,580 discloses that the sustained release formulation of somatotropin was prepared as a liposome type by using lipid-soluble materials such as alphatocopherol hemisuccinate Tris salt, phosphatidyl choline and phosphatidyl ethanolamine. And in U.S. Pat. No. 4,675,189, the sustained release formulation of somatotropin was prepared as a microcapsule type by using biocompatible polymer. And in U.S. Pat. No. 4,857,506, the sustained release formulation of somatotropin was prepared as a multiple water-in oil-in water(W/O/N) emulsion type. But somatotropin formulations according to these techniques are inadequate to be commercialized since the formulations have short duration of action or very complicated manufacturing processes requiring high techniques, and low stability as well as low recovery rate of making somatotropin into a desired form.
By using quite different techniques, implantable formulations, which are solid dosage forms, were prepared for improving the sustained release of somatotropin. These techniques have been described in U.S. Pat. No. 4,452,775, U.S. Pat. No. 4,761,289, U.S. Pat. No. 4,765,980, U.S. Pat. No. 4,774,091, U.S. Pat. No. 4,786,501, U.S. Pat. No. 4,863,736, U.S. Pat. No. 5,035,891, U.S. Pat. No. 5,198,422, U.S. Pat. No. 5,228,697, U.S. Pat. No. 5,356,635, U.S. Pat. No. 5,595,752 and EP 246540 and 462959, and PCT/US92/01877, PCT/US91/08129, PCT/US90/01340, PCT/AU87/00139 and the like. These techniques tried to secure sustained release of somatotropin by implanting somatotropin into the animal body by surgical operation using an expensive device, or implanting a compressed somatotropin form into the animal body using a special implant apparatus. These implanting techniques are preferred for obtaining a desirable release amount and sustained effect of somatotropin. However, the implanting process is too difficult to be performed on animals and animals also feel very uncomfortable due to the foreign substance.
U.S. Pat. No. 5,520,927 and Korean Patent No. 177306 attempted to lengthen duration of action of somatotropin using tocopherol acetate which has been used as an antioxidant to prevent oxidation reaction of drugs which may occur in a somatotropin composition simply containing oils as described above. However, since the viscosity of tocopherol acetate or vitamin A dramatically increases as the temperature decreases, the somatotropin composition shows such poor syringeability that cannot be used in winter or cold areas, or immediately after being taken out of a refrigerator which is the storage condition of the somatotropin composition. Thus, it needs several tens of minutes to melt the composition under ambient temperature before use. Further, the syringeability under ambient temperature is not so good that it requires the great effort and long time for injection of the composition, resulting in doubling the pain of animal being administered.
The inventors of the present invention have conducted intensive researches to solve the above-mentioned problems of conventional somatotropin formulations.
SUMMARY OF THE INVENTION
The present inventors have developed a somatotropin-containing composition which can be administered into the body by injection that is the most general administration method hitherto as well as which can be injected with superior syringeability, even in winter at lower temperatures or immediately after being taken out of a refrigerator which is the storage condition of a somatotropin composition, and which has the same or better sustained release effect and physiological activity of somatotropin as those of conventional somatotropin formulations. The composition of the present invention is inherently in suspension form and consists of somatotropin, at least one lipid-soluble vitamin and at least one pharmaceutically acceptable lubricant.
An object of the present invention is to provide a composition comprising somatotropin and vitamins with improved syringeability, which can be more easily administered into body by injection that is the most general administration method hitherto, which can decrease injection frequency resulting in reducing the labor and cost for administration as well as animals pain, and which can increase the reproduction efficiency and the productivity of milk according to administration of somatotropin, while decrease the incidence of mastitis and metabolic diseases, by administering somatotropin with vitamins simultaneously, not separately.
Another object of the present invention is to provide a composition comprising somatotropin, which can be used in cold areas or in winter as well as immediately after being taken out of a refrigerator that is the storage condition of somatotropin composition, and which can be administered without difficulty due to o

Affiliated with

Also associated with

Rating

Somatotropin composition with improved syringeability does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Somatotropin composition with improved syringeability, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Somatotropin composition with improved syringeability will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3188466