Takeda Chemical Industries, Inc.

Yutaka Yamagata

Masafumi Misaki

Susumu Iwasa

Yasutaka Igari

Hiroaki Okada

Katsumi Iga

Kazumichi Yamamoto

Kayoko Okamoto

Shigeyuki Takada

Naoki Asakawa

Satoshi Iinuma

Takayuki Doen

A process for conveniently producing a stable protein powder retaining the higher-order structure at a high level which comprises freezing a protein-containing solution at a cooling rate of about &minus;300 to &minus;10&deg; C./min. and then drying.

Proces for producing protein powder

A method for producing a sustained-release preparation, which comprises dispersing a physiologically active polypeptide into an organic solvent solution of a biodegradable polymer and removing the organic solvent, wherein the polypeptide is a powder obtained by lyophilizing an aqueous solution of the polypeptide which solution has a water-miscible organic solvent and/or a volatile salt; which improves the ease of handling of the physiologically active polypeptide powder in the process for producing the preparation; which makes it possible to industrially produce the sustained-release preparation in large scale; which provides a sustained-release preparation showing high and stable concentration of the active component in blood in long term, low initial release ratio of the physiologically active polypeptide, and high entrapment ratio of the polypeptide into the sustained-release preparation.

Sustained-release preparation of physiologically active polypeptide and production thereof

The present invention provides a complex of human growth hormone and zinc containing human growth hormone and zinc at a molar ratio of about 1:1.6 to about 1:2.4, and a sustained-release preparation which comprises the complex of human growth hormone and zinc and a biodegradable polymer and which has a high entrapment ratio of human growth hormone and exhibits a stable sustained-release suppressing the initial burst.

Complex of human growth hormone and zinc and use

A method of producing sustained-release microcapsules which comprises dispersing a physiologically active polypeptide into a solution of a biodegradable polymer and zinc oxide in an organic solvent, followed by removing the organic solvent; which provides a sustained-release preparation showing a high entrapment ratio of the physiologically active polypeptide and its constant high blood concentration levels over a long period of time.

Method of producing a sustained-release preparation

According to a first embodiment, there is provided a sustained-release preparation comprising a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble physiologically active substance which is not an endothelin antagonist, and a biodegradable polymer. The sustained-release preparation of the first embodiment is highly efficient in incorporating the water-soluble physiologically active substance and suppresses the initial burst of the water-soluble physiologically active substance. The sustained-release preparation of the present invention is capable of releasing the water-soluble physiologically active substance while retaining its bioactivity after administration in vivo. Furthermore, the water-soluble physiologically active substance in the sustained-release preparation is kept stable for a long period of time, with little loss of bioactivity. According to a second embodiment, there is provided a sustained-release preparation comprising an anti-endothelin substance and a biodegradable polymer. The sustained-release preparation of the present invention sustainedly releases an anti-endothelin substance, serving well in the treatment of endothelin-associated diseases.

Sustained-release preparation

This invention provides a sustained-release preparation comprising a biodegradable polymer metal salt and broactive polypeptide, with enhanced entrapment of the bioactive polypeptides, a suppression of initial burst, and a constant long-term release of the bioactive polypeptides.

Method of producing sustained-release preparation

Complex of human growth hormone and zinc

A parenteral pharmaceutical preparation comprises a matrix containing a physiologically active peptide or protein and a polyglycerol diester of a saturated fatty acid, and the matrix is in a solid form at room temperature. The molecular weight of the physiologically active peptide or protein is 2,000 dalton or more. The saturated fatty acid includes fatty acids having about 16 to 30 carbon atoms such as palmitic acid, stearic acid, etc. The matrix may be in a pillar or granular form. The parenteral pharmaceutical preparation can be used as an injectable solid administered subcutaneously or intramuscularly (for example, a pellet or tablet for implantation), a suppository or the like, and can release the physiologically active peptide or protein sustainedly for a prolonged period of one week or more.

Sustained releasable parenteral pharmaceutical preparations and method

A method of producing a sustained-release preparation which includes permitting a water-soluble polypeptide to permeate into a biodegradable matrix in the aqueous solution. The production method of the present invention makes possible the permeation of a water-soluble polypeptide into a biodegradable matrix without bringing the water-soluble polypeptide into contact with an organic solvent. Hence the water-soluble polypeptide is prepared without affecting the water-soluble polypeptide bioactivity and is thus effective for use as a pharmaceutical.

Growing community of inventors

Kobe, Japan

Yutaka Yamagata