Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-10-26
2002-04-23
O'Sullivan, Peter (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C424S489000, C424S490000, C424S491000, C424S497000, C424S499000, C514S001000, C514S012200, C530S399000
Reexamination Certificate
active
06376461
ABSTRACT:
The following disclosure through page 31 relates to a first embodiment of the present invention.
TECHNICAL FIELD OF THE FIRST EMBODIMENT
The first embodiment of the present invention relates to a sustained-release preparation which comprises a water-insoluble or a slightly water-soluble polyvalent metal salt of a water-soluble peptide type of physiologically active substance which is not an endothelin antagonist, and a biodegradable polymer.
BACKGROUND ART OF THE FIRST EMBODIMENT
Physiologically active substances, particularly peptides or derivatives thereof, are known to exhibit various pharmacologic actions in vivo. Some have been produced in large amounts, for pharmaceutical application, by chemical synthesis, or as a result of advances in gene engineering and cell engineering technologies, using organisms such as
Escherichia coli
, yeasts, animal cells and hamsters. However, these peptides must be administered frequently, since they generally have a short biological half-life, and so pose a significant physical burden of injection on patents. To solve this problem, various attempts have been made to develop sustained-release preparations.
The first problem to solve in developing a sustained-release preparation of a water-soluble physiologically active substance, particularly a water-soluble peptide (hereinafter also referred to as “peptide”) is to control peptide solubility, i.e., to regulate the peptide release rate.
Japanese Publication of the Translation of International Patent Application No. 500286/1991 discloses an insoluble zinc-protamine-&agr;-interferon complex.
Japanese Patent Unexamined Publication No. 2930/1988 discloses a system comprising a polylactide in which a macromolecular polypeptide is dispersed.
Japanese Patent Unexamined Publication Nos. 221855/1993 and 172208/1994 disclose a technology by which a water-soluble peptide is converted to a water-insoluble peptide salt, which is then suspended in an organic medium containing a biodegradable polymer to efficiently incorporate the water-soluble peptide in fine grains. The water-insoluble peptide used in these patent publications is an organic acid salt formed at the base portion of the water-soluble peptide molecule, and is exemplified by pamoate, tannic acid, stearic acid or palmitate.
Although there have been various attempts to produce sustained-release preparations of water-soluble physiologically active substances, as stated above, no satisfactory sustained-release preparations have been obtained; there is therefore need for the development of a sustained-release preparation that is highly efficient in incorporating water-soluble physiologically active substance, suppresses initial water-soluble physiologically active substance burst, offers a constant water-soluble physiologically active substance release rate, and keeps the bioactivity of water-soluble physiologically active substance.
DISCLOSURE OF THE FIRST EMBODIMENT
Through extensive investigation to solve the above problems, the present inventors found that a sustained-release preparation, having dramatically increased efficiency of water-soluble peptide type of physiologically active substance except for an endothelin antagonist incorporation in a biodegradable polymer and showing little drug burst just after administration to the living body, can be obtained by producing a water-insoluble or a slightly water-soluble polyvalent metal salt of a water-soluble peptide type of physiologically active substance except for an endothelin antagonist (hereinafter also referred to as “complex”), which salt is formed from a combination of a water-soluble peptide type of physiologically active substance except for an endothelin antagonist having an acidic group, or a water-soluble salt thereof (hereinafter also referred to as “physiologically active substance”), with a water-soluble polyvalent metal salt, and dispersing or dissolving it in a biodegradable polymer. After further investigations based on this finding, the inventors developed the present invention.
Accordingly, the present invention relates to:
(1) a sustained-release preparation which comprises
(a) a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble peptide type of physiologically active substance except for an endothelin antagonist and
(b) a biodegradable polymer,
(2) a preparation of term 1 above, wherein the physiologically active substance is a water-soluble peptide or a derivative thereof,
(3) a preparation of term 2 above, wherein the peptide is a hormone, cytokine, hematopoietic factor, growth factor, enzyme, soluble or solubilized receptor, antibody, antigen containing peptide, blood coagulation factor or adhesion molecule,
(4) a preparation of term 2 above, wherein the peptide is a hormone,
(5) a preparation of term 4 above, wherein the hormone is a growth hormone
(6) a preparation of term 3 above, wherein the hormone is an insulin,
(7) a preparation of term 2 above, wherein the peptide is a cytokine,
(8) a preparation of term 7 above, wherein the cytokine is an interferon,
(9) a preparation of term 2 above, wherein the peptide is a growth factor,
(10) a preparation of term 1 above, wherein the polyvalent metal salt is a transition metal salt,
(11) a preparation of term I above, wherein the polyvalent metal salt is a zinc salt,
(12) a preparation of term 1 above, wherein the solubility of the polyvalent metal salt to water is about 0 to about 0.1% (w/w) at 20° C.,
(13) a preparation of term 1 above, wherein the solubility of the polyvalent metal salt to water is about 0 to about 0.01% (w/w),
(14) a preparation of term 1 above, which contains about 0.1 to about 50% (w/w) of the polyvalent metal salt,
(15) a preparation of term 1 above, which contains about 1 to about 30% (w/w) of the polyvalent metal salt,
(16) a preparation of term 1 above, wherein the biodegradable polymer is an aliphatic polyester,
(17) a preparation of term 16 above, wherein the aliphatic polyester is a polymer of lactic acid and glycolic acid,
(18) a preparation of term 17 above, wherein the composition ratio of lactic acid and glycolic acid is 100/0 to about 40/60 (mole %),
(19) a preparation of term 18 above, wherein the composition ratio is about 90/10 to about 45/55 (mole %),
(20) a preparation of term 17 above, wherein the weight-average molecular weight of the polymer is about 3,000 to about 20,000,
(21) a preparation of term 17 above, wherein the weight-average molecular weight of the polymer is about 3,000 to about 14,000,
(22) a preparation of term 16 above, wherein the alihatic polyester is a homopolymer of lactic acid,
(23) a preparation of term 22 above, wherein the weight-average molecular weight of the homopolymer is about 3,000 to about 20,000,
(24) a preparation of term 22 above, wherein a weight-average molecular weight of the homopolymer is about 3,000 to about 14,000,
(25) a preparation of term 1 above, wherein the preparation is a microcapsule,
(26) a preparation of term 25 above, wherein the microcapsule is for injection,
(27) a preparation of term 1 above, which is an injectable one,
(28) Use of a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble peptide type of physiologically active substance except for an endothelin antagonist and a biodegradable polymer for the production of a sustained-release preparation, and
(29) a method of producing a sustained-release preparation, which comprises dispersing a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble peptide type of physiologically active substance except for an endothelin antagonist in an oil phase containing a biodegradable polymer to make a solid-in-oil emulsion, adding the solid-in-oil emulsion to a water phase to make a solid-in-oil-in-water emulsion, and then in-water drying the soild-in-oil-in-water emulsion.
Incidentally abbreviations of amino acid, peptide or the like used in the present invention are based on those in accordance with IUPAC-IUB Commission on Biochemical Nomenclature or those conventionally used in the relevant field
Igari Yasutaka
Iinuma Satoshi
Okada Hiroaki
Yamagata Yutaka
Yamamoto Kazumichi
O'Sullivan Peter
Takeda Chemical Industries Ltd.
LandOfFree
Sustained-release preparation does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sustained-release preparation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sustained-release preparation will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2888286