AU636653B2 - Stabilized leukocyte-interferons - Google Patents
Stabilized leukocyte-interferons Download PDFInfo
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- AU636653B2 AU636653B2 AU63098/90A AU6309890A AU636653B2 AU 636653 B2 AU636653 B2 AU 636653B2 AU 63098/90 A AU63098/90 A AU 63098/90A AU 6309890 A AU6309890 A AU 6309890A AU 636653 B2 AU636653 B2 AU 636653B2
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- Australia
- Prior art keywords
- composition according
- vol
- interferon
- ifn
- bile
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Description
63 S F Ref: 139634 FORM COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 COMPLETE SPECIFICATION
(ORIGINAL)
FOR OFFICE USE: Class Int Class Complete Specification Lodged: Accepted: Published: Priority: Related Art: Name and Address of Applicant: Address for Service: F.Hoffmann-La Roche AG 124 Grenzacherstrasse CH-4002, Basel
SWITZERLAND
Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia Complete Specification for the invention entitled: Stabilized Leukocyte-Interferons The following statement is a full description of this invention, including the best method of performing it known to me/us 5845/16 1- ES 4100/73 Abs tract The stabilization of human interferon with disaiccharides and optionally bile acids or bile acid deri.vatives.
-1 A RAN 4100/73 The present invention is concerned with the stabilization of leucocyte interferon (IFN-a), especially in the form of lyophilizates, using disaccharides and optionally bile acids or bile acid derivatives.
Under IFN-a there is to be understood a body- -specific protein having antiviral and immunoregulatory acl.ivity. The antiviral effect is achieved not by a direct influence on the viruses themselves, but by an activity on their target cells in the sense of a protection against the viral infection. In addition to the antiviral 1 activity, a-interferon can exert objectifiable effects on cancer tumors, which makes it suitable for use in cancer therapy, and it influences the immune system of the body in that e.g. it activates macrophages and NK cells and increases the expression of various immunologically si.gnificant constituents of the cell membrane.
Thanks to recombinant DNA technology, IFN-a can today be prepared in a microbiological manner in amounts which hitherto could not be made available by isolation from natural material (leucocytes, lymphocytes) and purification in spite of the greatest efforts.
This new technology has opened for the first time a way for the intensive clinical testing and possible wide therapeutic use of IFN-a and has made possible an adequate supply of the active substance for persons seeking a treatment with the active substance.
Ar/5.7.90 2 It has now emerged that IFN-a in pure form is not completely stable and suffers loss of its biological activity during storage.
Different adjuvants have therefore already been used for the stabilization of IFN-a. A certain stabilization of IFN-a has been achieved by the addition of glycine (noe e.g. publ. PCT Application 86/00531 and European Patent, Publ. No. 82 481), whereby, however, albumin is preferably simultaneously added.
In efforts to achieve a good stabilization of IFN-c over the longest possible period while avoiding the use of high-molecular compounds such as serum albumin, gelatine, dextran or starch derivatives, it has been found that this is successful using disaccharides and optionally bile acids or bile acid derivatives.
The present invention is accordingly concerned with compositions, especially in the form of lyophilizates, which contain a disaccharide and optionally bile acids or bile acid derivatives, as well as a process for their manufacture which comprises treating an IFN-a solution with a disaccharide and optionally bile acids or bile acid derivatives and, if desired, lyophilizing the solution obtained. The present invention is also concerned with pharmaceutical preparations based on the compositions in accordance with the invention as well as the use of disaccharides and optionally bile acids or bile acid derivatives for the stabilization of IFN-a.
The compositions in accordance with the inventi.on can be used for the manufacture of a pharmaceutical preparation for the therapy or prophylaxis of a large number of infections and immunoregulatory anomalies, especially neoplasms.
3 The stabilization can be applied to natural or recombinant IFN-a (r-IFN-a). Recombinant IFN-aA (r-IFN-aA) is an eopecially preferred IFN-a i.n connection with the present invention. The content of TFN-a in the compositions in accordance with the invention is not critical. The concentraLton range extends over more .han the power of ten and is limited at the upper end o;c entially only by the solubility of IFN-a.
Tn Lhe cane of human TFN-a there come into 8 consideration, for example, concentriations up to 5*10 international units with a preferred range 6 8 being 0.1 x 10 to 1 x 10 I.U./ml, especially 1 x 10 6 to 5 x 107 I.U./ml.
The disaccharide, preferably lactose or saccharose, is added .o the IFN-a solut.ion in a concentration of to 15% preferably 5% (wt./vol.).
The bile acids or the bile acid derivatives can be e.g. cholic acid, deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, chenodeoxycholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, glycocholic acid or taurocholic acid, with glycocholic acid being especially preferred. It is added to the IFN-a solution in a concentration of 0.01 to 3% preferably 0.5% (wt./vol.).
Further adjuvants for the pH-adjustment, e.g. NaOH, pH-buffering, e.g. phosphate buffer and citrate buffer, isotonization, e.g. sodium chloride, and preservation of the preparati.on, e.g. methyl p-hydroxybenzoate and propyl p-hydroxybenzoate, as well as for strengthening the structure of the lyophilizate, e.g. glycine, can also be added.
Particulars of the invention are described in the following Examples.
4 The r-IFN-A used in the Examples can be obtained in pure form according to known procedures described in the literature or according to procedures obvious to a person skilled in the art.
In order to determine the antiviral activity of the r-IFN-aA, there was used a cytopathological test with MDBK (Madison Darby Bovine Kidney) cells and VSV (vesicular stomatitis virus) viruses, which has been described by Rubinstein et al. Virol. 37, 755-758 (1981)]. MDBK cells and VSV viruses are generally accessible and can be obtained e.g. from the American Type Culture Collection S (ATCC) (MDBK: ATCC Nos. CCL 21 and CRL 6071; VSV: ATCC No. VR-1 59).
For the stability testing, solutions with r-IFN-aA and the additives under investigation were lyophilized and stored at different temperatures (50, 25 350, 450, 550 and 65 0 After fixed time intervals the antiviral activity of the IFN-aA still present in the lyophilizates was determined.
The following Examples illustrate the invention without limiting it.
Example 1 3 mio. I.U. of r-IFN-aA were taken up in 1 ml of water containing human serum albumin, glycine or lactose and optionally further adjuvants (see Table The solutions obtained were sterile-filtered (membrane filter, 0.2 um pore size) and loaded in 10 ml glass vials in a steam-sterilized freeze-dryer. After freezing the solutions at -40 0 C during 4 h the primary drying of the lyophilization process was carried at about -30°C under a pressure of 0.1 mbar during 14 h. Subsequently, the 5 secondary drying was carried out under a full vacuum at 0 °C during about 4 h. The glass vials were closed with suitable aluminium caps in the freeze-dryer under a N 2 atmosphere. They were subsequently subjected to different stability tests, the results of which are compiled in Table 1.
Oh -6 Table 1 Composition of the lyophilizates containing r-IFN-a.A Lyophilizate from: r-IFN-cxA (mio. 3.0 Sodium chloride (mg) Human serum albumin (mg) Mainitol pyrogen-free (mg) Glycine (mg) Lactose (mg) NaH 2P0 4 H 20 ad pH 7.4 NaOH 1N ad pH 7.4 2 3 3.0 3.0 20.0 50.0 q. s. 4 3.0 20.0 1.0.0 q. s.
q. s. q. s.
.0 ml 1.0 ml 1.0 ml Water for injection Antiviral activity (in mio. after 1. 0 ml 1 1. 0 ml manufacture of lyophil izate 2 weeks! S 0
C
11/25 0
C
11/35 0
C
11/45 0
C
11/55 0
C
0
C
3 months/ 5 0
C
11 /25 0
C
11 /35 0
C
11 /45 0
C
6 months! 5 0
C
It /25 0
C
11 /35 0
C
11 /45 0
C
the 3.0 3.0 2.7 3 .3 2.3 3. 2 3.2 3. 3 2.7 2.8 2.1 2.7 2.5 2.4 1.7 3.0 2.7 2.8 2.0 1.5 0.6 2.5 2.3 2.1 1.2 3. 1 3.1 1.9 1.7 2. 8 3.4 3 .3 3.0 2.4 3. 3 1. 8 3. 1 2.7 1.2 2. 9 0.9 2. 1 0.8 0.4 3.0 3.1 3 .1 2.8 3.2 3.
3.0 3.0 3.6 3.2 2.7 1.3 3 .1 2.4 2.4 1. 1 3.5 3.3 2.6 n. t.
-7 12 months! 5 0
C
0
C
3.7 n. t.
2. 9 n. t.
2. 1 n. t.
n. t. n. t.
3.0 2.9 2.7 2.7 2.8 1. 3 1.6 n~t. =not tested q.s. quantum satis 8 The best results were achieved with the lactose- -containing lyophilizate (see column This preparation exhibited an outstanding stability even after long-term storage at the storage temperature of 450C, which is almost prohibitive for IFN-. This result could also be confirmed unequivocally in experiments with lyophilizates containing 1 mio. I.U. of r-IFN-aA (see Table 2).
c 9- Table 2 Composition of the 1yophilizates containing r-IFN-cxA 1 2 Lyophilization from: r-IFN-o.A (mio. 0 5 Glycine (mg) 10.0 Lactose (mg) -50.0 NaQH 1N ad pH 7.4 q.s. q.s.
Water for injection 1.0 ml 1.0 ml Antiviral activity (in mio. after manufacture of the lyophilizate 0.4 0.4 2 weeks! 5 0 C 0.5 0.4 1/25 0 C 0.4 0.4 1/35 0 C 0.4 0.4 1/45 0 C 0.3 0.3 0 C 0.2 0.3 3 months! 5 0 C 0.5 3It /25 0 C 0.4 0.4 It /35 0 C 0.3 0.4 It /45 0 C 0.2 0.4 6 months! 5 0 C 0.4 11 /25 0 C 0.4 0.4 It /35 0 C 0.2 0.4 11 /45 0 C 0.05 0.3 10 Example 2 The stability of lyophilizates containing r-IFN-aA and saccharose was investigated in an analogous manner to Example 1. It was established that the stabilization of r-IFN-aA obtained with lactose can also be achieved with saccharose (see Table 3).
A
Mft 11 Tlable 3 composition of the lypiiaescnann r-IFN-ctA Lyophilizate from: r-IFN-aA (mio. I.U.) Sodium chloride (mg) Human serum albumin Glycine Saccharose (mg) NaR P0 H 20 ad pH 7.4 NaOH IN ad pH 7.4 Water for injection ad 3 20.0 10. 0 50.0 q. s.q. s.
1. 0 ml 1. 0 ml 1. 0 ml Antiviral activity (in mio. after manufacture of lyophilizate 3 months! 5 0
C
11 /25 0
C
11 /35 0
C
11 /45 0
C
6 months! 5 0
C
11 /25 0
C
[I /35 0
C
I /45 0
C
the 2.7 2.7 2. 5 2.4 1.7 3.5 3.3 2.6 3.0 2. 5 2.3 2.1 1.2 3 .1 3.1 1.9 1.7 3.4 3 .9 3. 6 3.7 3.7 3.7 12 Example 3 The stability of lyophilizates containing r-IFN-aA in high concentrations and lactose or saccharose was investigated in an analogous manner to "-ample 1. It was established that the stabilization of -a produced using disaccharides can also be achieved in the case of high rIFN-aA concentrations (see Table 4).
13 Table 4 Composition of lyophilizates containing r-IFN-c.A Lyophilized from: 1 2 3 4 r-IFN-cxA (mio. 9.0 9.0 18.0 18.0 Lactose 50.0 mg 50.0 mng Saccharose 50.0 mg 50.0 mg Glycine 10.0 mg 10.0 mg 10.0 mug 10.0 mug NaOH 1N ad pH 7.4 q.s.
Water for injection ad 1.0 ml 1.0 ml 1.0 ml 1.0 Ml Antiviral activity (in mio. after manufacture of the lyophilizate 8.8 8.9 18.3 19.9 3 months! 5 0 C 9.9 9.6 17.8 23.4 11 /25 0 C 10.0 10.5 19.1 23.2 11 /35 0 C 10.3 10.1 20.5 n.t.
11 /45 0 C 10.4 10.9 22.0 n.t.
6 months! 5 0 C 9.7 n.t. 17.8 19.1 3 1 /25 0 C 9.9 n.t. 21.1 21.9 30/5C8. 166nt 11 /45 0 C 8.9 n.t. 16.6 n.t.
14 Example 4 The stability of lyophilizates containing r-*IFN-c-A, lactose and glycocholic acid was investigated in an analogous riinnec to Example 1. The results obtained are compiled in Table 15 Table (2omposjlion of the 1yoihilizates containing r-IFN-aLA lyophilizate from: r-IFN-u (rnio. 1 3 9 18 Glycocholic acid (mg) 5.0 5.0 5.0 Lactose (mg) 50.0 50.0 50.0 50.0 Sodium chloride (mg) 2.5 2. 5 2.5 NaOH 1N ad pHl 7.4 q.s. q.s. q.s. q.s.
Water for injecl.iofl ad 1.0 ml 1.0 ml 1.0 ml1 1. 0 ml Anl~sviral. activity (in mnio. after manufacture of the lyophilizate 0.96 2.97 8.56 18.8 14 days! 5 0 C 0.85 1/ RT 0.92 0 C 0.85 11/45 0 C 0.83 6 moniths! 5 0 ;C 1.02 2.89 9.2 18.7 11 Ri' 1.1 2.82 8.7 18.7 11 /35 0 C 1.06 3.11 8.9 18.3 11 /45 0 C 0.99 2.71 8.94 n.t.
Claims (17)
1. A composition containing a-interferon, a disaccharide and optionally bile acids or bile acid derivatives.
2. A composil.ion according to claim 1, wherein the a-interferon is a natural or a recombinant human loucocyte interferon.
3. A composition according to claim 2, which contains r-IFN-aA.
4. A composi Lion according to any one of claims 1 to S3 in the form of a lyophilizate. A composition according to any one of claims 1 to 4, whorein the disaccharide is lactose or saccharose.
6. A composition according to any one of claims 1 to which contains 0.5% to 15% (wt./vol.) of lactose or saccharose.
7. A composition according to any one of claims 1 to 5, which contains 5% (wt./vol.) of lactose or saccharose.
8. A composition according to any one of claims 1 to 6, which contains 0.01% to 3.0% (wt./vol.) of bile acids or bile acid derivatives, preferably 0.1% to 1.0% (wt. vol.) of glycocholic acid.
9. A composition according to any one of claims 1 to 6, which contains 0.5% (wt./vol.) of bile acid derivatives, preferably 0.5% (wt./vol.) of glycocholic acid. 17 A composition containing r-IFN-aA, 5% (wt./vol.) of lactose and 0.5% (wt./vol.) of glycocholic acid.
11. A composition according to any one of claims 1 to 10 as a pharmaceutically active material.
12. A composition according to any one of claims 1 to 10 as an antivirally and immunoregulatory active material.
13. A process for the manufacture of a composition according to any one of claims 1 to 10, which process comprises treating a-interferon with a disaccharide and optionally bile acids or bile acid derivatives, preferably glycocholic acid, and, if desired, lyophilizing the solution obtained.
14. A pharmaceutical preparation comprising a composition according to any one of claims 1 to 10, together with a pharmaceutically acceptable carrier, diluent and/or excipient. -J. A r I- LMM/1662u L 18 The use of disaccharides and optionally bile acids or bile acid derival.ives, preferably glycocholic acid, for the stabilization of a-interferon.
16. The use of a composition according to any one of claims 1-10 for the manufacture of a pharmaceutical preparation for the therapy or prophylaxis of illnesses.
17. The use of a composition according to any one of claims 1-10 for the manufacture of a pharmaceutical preparation for the therapy or prophylaxis of viral infections.
18. The use of a composition according t.o any one of claims 1-10 for the manufacture of a pharmaceutical preparation for the therapy or prophylaxis of immuno- regulatory anomalies.
19. The use of a composition according to any one of claims 1-10 for the manufacture of a pharmaceutical preparation for the therapy or prophylaxis of neoplasms. 19 A composition containing a-interferon, a disaccharide and optionally bile acids or bile acid derival.ves propared accordi~ng to a process as claimed in claim 13. 20
21. A composition containing ac-interferon, a disaccharide and optionally bile acids or bile acid derivatives, substantially as hereinbefore described with reference to any one of the Examples. DATED this THIRD day of MARCH 1993 F.Hoffmann-La Roche AG Patent Attorneys for the Applicant SPRUSON FERGUSON LLMM/1662u
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH351489 | 1989-09-28 | ||
CH3514/89 | 1989-09-28 |
Publications (2)
Publication Number | Publication Date |
---|---|
AU6309890A AU6309890A (en) | 1991-04-11 |
AU636653B2 true AU636653B2 (en) | 1993-05-06 |
Family
ID=4257630
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU63098/90A Expired - Fee Related AU636653B2 (en) | 1989-09-28 | 1990-09-21 | Stabilized leukocyte-interferons |
Country Status (26)
Country | Link |
---|---|
EP (1) | EP0420049B1 (en) |
JP (1) | JPH03130232A (en) |
KR (1) | KR910005886A (en) |
CN (1) | CN1050503A (en) |
AR (1) | AR244551A1 (en) |
AT (1) | ATE92334T1 (en) |
AU (1) | AU636653B2 (en) |
CA (1) | CA2024046A1 (en) |
CZ (1) | CZ277712B6 (en) |
DD (1) | DD298054A5 (en) |
DE (1) | DE59002183D1 (en) |
FI (1) | FI904756A0 (en) |
HU (1) | HU205555B (en) |
IE (1) | IE903479A1 (en) |
IL (1) | IL95769A0 (en) |
IS (1) | IS3631A7 (en) |
MC (1) | MC2149A1 (en) |
MX (1) | MX22522A (en) |
MY (1) | MY106615A (en) |
NO (1) | NO904218L (en) |
NZ (1) | NZ235153A (en) |
PH (1) | PH27531A (en) |
PT (1) | PT95454A (en) |
RU (1) | RU2008017C1 (en) |
YU (1) | YU184090A (en) |
ZA (1) | ZA907579B (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU6794194A (en) * | 1993-05-18 | 1994-12-20 | Bukh Meditec A/S | A method for the preparation of interferons |
DK0920329T3 (en) * | 1996-05-09 | 2003-01-27 | Feronpatent Ltd | Stabilization of interferons in aqueous solution with gum arabic |
EP1007083A1 (en) * | 1997-05-09 | 2000-06-14 | Feronpatent Limited | Stabilisation of interferons in aqueous solution for manufacture of sublingually administered tablets |
US6180096B1 (en) | 1998-03-26 | 2001-01-30 | Schering Corporation | Formulations for protection of peg-interferon alpha conjugates |
EP1066059B1 (en) * | 1998-03-26 | 2005-06-15 | Schering Corporation | Formulations for protection of peg-interferon alpha conjugates |
CN1175901C (en) * | 1999-12-06 | 2004-11-17 | 天津华立达生物工程有限公司 | Stable water solution of interferon |
DE602005022895D1 (en) | 2004-08-12 | 2010-09-23 | Schering Corp | STABLE PEGYLATED INTERFERON FORMULATION |
DE102004048379A1 (en) | 2004-10-01 | 2006-04-13 | "Stiftung Caesar" (Center Of Advanced European Studies And Research) | Spring element made of sputtered shape memory alloy |
CU23432B6 (en) * | 2005-11-02 | 2009-10-16 | Ct Ingenieria Genetica Biotech | STABILIZED FORMULATIONS CONTAINING GAMMA AND ALFA INTERFERONS IN POTENTIAL PROPORTIONS |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5821691A (en) * | 1981-07-29 | 1983-02-08 | Mochida Pharmaceut Co Ltd | Purifying method of interferon |
EP0080879B1 (en) * | 1981-11-28 | 1986-10-01 | Sunstar Kabushiki Kaisha | Pharmaceutical composition containing interferon in stable state |
ATE31023T1 (en) * | 1983-04-28 | 1987-12-15 | Armour Pharma | PHARMACEUTICAL PREPARATION CONTAINING PURIFIED FIBRINONECTIN. |
EP0133767B1 (en) * | 1983-08-04 | 1991-04-03 | The Green Cross Corporation | Gamma interferon composition |
MA20647A1 (en) * | 1985-03-25 | 1986-10-01 | Schering Corp | STABLE COMPOSITIONS BASED ON INTERFERON-GAMMA |
US4816568A (en) * | 1986-05-16 | 1989-03-28 | International Minerals & Chemical Corp. | Stabilization of growth hormones |
-
1990
- 1990-08-27 CA CA002024046A patent/CA2024046A1/en not_active Abandoned
- 1990-09-03 NZ NZ235153A patent/NZ235153A/en unknown
- 1990-09-06 CZ CS904328A patent/CZ277712B6/en unknown
- 1990-09-20 DE DE9090118132T patent/DE59002183D1/en not_active Expired - Fee Related
- 1990-09-20 EP EP90118132A patent/EP0420049B1/en not_active Expired - Lifetime
- 1990-09-20 AT AT90118132T patent/ATE92334T1/en not_active IP Right Cessation
- 1990-09-21 ZA ZA907579A patent/ZA907579B/en unknown
- 1990-09-21 AU AU63098/90A patent/AU636653B2/en not_active Expired - Fee Related
- 1990-09-24 HU HU906021A patent/HU205555B/en not_active IP Right Cessation
- 1990-09-24 MC MC902149A patent/MC2149A1/en unknown
- 1990-09-24 MX MX2252290A patent/MX22522A/en unknown
- 1990-09-25 IL IL95769A patent/IL95769A0/en unknown
- 1990-09-26 PH PH41267A patent/PH27531A/en unknown
- 1990-09-26 DD DD90344228A patent/DD298054A5/en not_active IP Right Cessation
- 1990-09-26 MY MYPI90001656A patent/MY106615A/en unknown
- 1990-09-26 AR AR90317958A patent/AR244551A1/en active
- 1990-09-27 NO NO90904218A patent/NO904218L/en unknown
- 1990-09-27 FI FI904756A patent/FI904756A0/en not_active IP Right Cessation
- 1990-09-27 JP JP2258806A patent/JPH03130232A/en active Pending
- 1990-09-27 CN CN90108133A patent/CN1050503A/en active Pending
- 1990-09-27 PT PT95454A patent/PT95454A/en not_active Application Discontinuation
- 1990-09-27 KR KR1019900015368A patent/KR910005886A/en not_active Application Discontinuation
- 1990-09-27 IS IS3631A patent/IS3631A7/en unknown
- 1990-09-27 IE IE347990A patent/IE903479A1/en unknown
- 1990-09-27 RU SU904831274A patent/RU2008017C1/en active
- 1990-09-28 YU YU184090A patent/YU184090A/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU6309890A (en) | 1991-04-11 |
PH27531A (en) | 1993-08-18 |
RU2008017C1 (en) | 1994-02-28 |
IE903479A1 (en) | 1991-04-10 |
CS432890A3 (en) | 1992-12-16 |
JPH03130232A (en) | 1991-06-04 |
AR244551A1 (en) | 1993-11-30 |
HUT56284A (en) | 1991-08-28 |
EP0420049A1 (en) | 1991-04-03 |
ZA907579B (en) | 1991-06-26 |
ATE92334T1 (en) | 1993-08-15 |
CZ277712B6 (en) | 1993-03-17 |
NO904218L (en) | 1991-04-02 |
EP0420049B1 (en) | 1993-08-04 |
MX22522A (en) | 1993-10-01 |
MY106615A (en) | 1995-06-30 |
HU205555B (en) | 1992-05-28 |
CA2024046A1 (en) | 1991-03-29 |
IS3631A7 (en) | 1991-03-29 |
YU184090A (en) | 1992-09-07 |
IL95769A0 (en) | 1991-06-30 |
MC2149A1 (en) | 1992-03-10 |
HU906021D0 (en) | 1991-03-28 |
DE59002183D1 (en) | 1993-09-09 |
DD298054A5 (en) | 1992-02-06 |
NZ235153A (en) | 1993-03-26 |
NO904218D0 (en) | 1990-09-27 |
KR910005886A (en) | 1991-04-27 |
FI904756A0 (en) | 1990-09-27 |
CN1050503A (en) | 1991-04-10 |
PT95454A (en) | 1991-05-22 |
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