JP3048533B2 - Composition containing recombinant human γ-interferon for systematically treating allergic diseases at low dose - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] FIELD OF THE INVENTION The present invention relates to a low doseThat
Recombinant humans for systematic treatment of lugi diseaseγ-a
The present invention relates to an interferon-containing agent. [0002] 2. Description of the Related Art All known interferons are
Between the nucleotide sequences of the structural gene and its amino acids
Based on the homology between the sequences, there are three distinct groups,
That is, it is classified into α-IFN, β-IFN and γ-IFN.
It is. [0003] These used names are "Interface".
Elon Naming Committee "[J. Wilsek (1983)
By Archives of Virology, Vol. 77, No.
Pp. 283-285]
Is disgusted. In addition to the above main criteria, the γ-IFN group
To characterize, use the other groups of interferons and immunology
Does not cross-react with each other and what is α-IFN and β-IFN
Note that it shows biological instability at pH 2
Can be seen. [0004] γ-IFN stimulates whole leukocytes
According to the field of medicine, it is generally called buffy coat,
In a complex process with mitogens, antigens or specific antibodies,
For example, interleukin 1 (IL1), interleukin
2 (IL2), colony stimulating factor (CSF), migration inhibition
Factor (MIF), macrophage activating factor (MAF),
Tumor gangrene factor (TNF), lymphotoxin (LT) and
And many other factors such as fibroblast growth factor (FGF)
Produced with offspring (vehicle). These other factors are
-A. Georgiades and others
And its uses ”(P.E.
A. Carter), Springer Publishing (1984)
PH Waksman, "Lin
Photokin's Biology ”, S. Kochen et al., Academy
-It is described in Press Publishing (1979). [0005] SUMMARY OF THE INVENTION The present invention provides
Is neoplastic cell proliferationTreatγ-interferon
It is intended to provide an agent. [0006] SUMMARY OF THE INVENTION The present invention relates to a method for manufacturing a vehicle having a weight of about 60 kg.
Weight and 1.7m^TwoFor adult patients with body surface area
As a daily dose to be administered at intervals of days or months
100,000 to 2,000,000 International Standard Unit (IE) (approx.
(Equivalent to 200 μg) to treat human diseases systematically.
Disclose about γ-interferon-containing agents for placing
You. [0007] As formed by a subgroup of lymphocytes
Factors are commonly referred to as lymphokines. Γ-IFN is also included in this group
And is produced primarily by T-lymphocytes. γ-I
The synthesis itself of T-lymphocytes producing FN is also dependent on the above factors.
Affected by presence. Furthermore, γ-IFN is structurally
A current established or transformed cell line that produces
Was published by N. Fujii and other journals
G, Vol. 130, pp. 1683-1686.
And journal Imi by A-Trotnik
Synology, Vol. 131, pp. 794-800
Have been. Preferred method for obtaining human crude γ-IFN
Is described as follows: Preserved blood as starting material
Lymphocyte-rich plasma fraction, the so-called “buff
コ ー ト Coat ”and store it,
Separate from plasma debris by careful centrifugation at 800 g
You. Pellet whole leukocytes in pre-warmed medium
Suspend cells at a concentration of 5,000,000 cells / mL.
In a suitable culture vessel, a predetermined amount of this cell suspension is
Mitogens (eg phytohemagglutinin) and hormones
Boresters such as holobormyristylacetic acid (PM
A)) up to 70 hours on a shaker at 37 ° C. after addition
Incubate. The culture supernatant containing γ-IFN was centrifuged.
Can be collected and stored at 4 ° C until use.
it can. Generally, the product thus obtained is equivalent to 1 mL.
Γ-I of about 10,000 International Standard Units (IE)
Contains FN. [0009] The content of γ-IFN is determined by the CPE-reduction test.
In more appropriate standard cells (eg, WISH)
Using a test virus (eg, murine EMC)
Shonal Institute of Health (USA)
Of the product according to the standard Gg 23-901-530
Measured as virus activity. Another method for obtaining a γ-IFN preparation is
"Infection and Immunity" by WK Yip et al. (19
October 1981), Volume 34, pages 131 to 133, and
U.S. Pat. Nos. 4,376,821 and 4,376.
No. 822 and 4,460,685.
ing. A basic method for obtaining a human γ-IFN preparation
Another method is to convert the human structural gene into a suitable vector.
It is performed by introducing into a foreign host cell. These recombination
Genes may be structurally or
Expressed by addition. [0012] Even if the structural gene
A distinct amino acid sequence that results in the synthesis of a possible amino acid sequence.
Even if the nucleotide sequence is present, it may be produced by the host cell.
The γ-IFN molecule of the product produced is not necessarily naturally produced
Is not the same as γ-IFN. Unique by "post-processing"
The possibility of obtaining this change while maintaining action is a so-called
Expanded by protein design, its structural genes are
Or by biochemical synthesis or transformation
Can be A host cell for receiving a human gene;
Bacteria (eg E. coli) [eg
ー Gene, Vol. 28, 55-6 by Simmons
4 (1984)] as well as yeast (
For example, Saccharomyces cerevisiae)
Nucleic Aseed Research by Derink, etc.
Volume 11, pages 1819 to 1837 (1983)
Or eukaryotic cells (eg, Chinese hamsters)
Egg cells) [for example, by SJ
Losseding National Academy Sciences
USA, Vol. 80, pp. 4654-4658 (198
3)] or monkey cells [for example,
-Nature, No. 295, by W. Gray
Vol., Pp. 503-508 (1982).
] Can be used. Γ-IFN in any of these systems
Is 100,000 I./mL of culture solution. E. FIG. More than
Or accumulate in the host itself,
Accumulate to 25% of protein content. Γ-IFN product obtained by the above method
Accumulation or purification of the following methods, alone or in combination
Can be done by using: 1. Controlled porous glass (CPG) or silica gel
Le; 2. Gel filtration (eg AcA54 or Sephacel S
200); 3. Ion exchange chromatography (CM-Sepharose)
Or phosphocellulose or DEAE-cellulose
S); 4. Affinity chromatography (ConA-Sepharose)
Or poly-U-Sepharose or Cu-chelate
-Sepharose); 5. Immunoaffinity chromatography (anti-γ-IFN-
Sepharose); 6. HPLC (eg, with reversed phase material). Correspondence
The method is the same as that of KY-IP, et al.
Partial Purification and Characterization of Feron ", Proceedings
・ National Academy Sciences USA, 7th
8, 1601-1605 (1981) or
-Novic et al., EMBO Journal, Volume 2, 15
27-1530 (1983) or German Patent No. 3
No. 136166A. By appropriate combination, electrophoretically uniform
It is possible to purify
The highest specific activity has been between 100,000,000 and 2,000,000.
00,000,000 I.S. E. FIG. While the stated
The average value is between 10,000,000 and 50,000,000
I. E. FIG. It is. Conventionally, interferons (α-IFN, β-IFN
IFN, γ-IFN) are very different doses and administrations
Is being administered to patients by law. Once a week or
Multiple doses of about 10,000,000 I.D. E. FIG. Until
Is said to be a low dose, and 20,000,
00 to 50,000,000 I.O. E. FIG. High dose
It is called quantity. Early in the therapeutic use of interferon,
These biotechnological manufacturing methods did not exist.
The substance can only be used in very small amounts, and
00,000I. E. FIG. Can administer smaller doses
won. Higher doses may include α-IFN and β-IFN.
IFN since the mid 1970's and also γ-IF
N has been possible for 1-2 years. Since then,
3,000,000 I.S. in systematic treatment. E. FIG. Than
Lower doses are generally used for resistance and toxicity studies and pharmacology
Used for strategic research. For α-IFN and β-IFN, tumors
3,000,000 in systematic treatment of ulcers and viral diseases
000I. E. FIG. Doses up to or not effective
The above doses have been used [tumor: JM
Kirkwood and MS Ernstoff, JA
Internal Clinical Oncology, Volume 2, 336
~ 352 (1984); A. Billiau, Control
Ludo Oncology, Volume 20, pages 251-269
(1984); E.M.Bonnem and R.J.
Wee Spiegel, Journal Biological Squirrel
Pective Modification, Volume 3, 580
598 (1984); Viral disease: T.C.
Merrigan et al. Engl, J.A. Med, Vol. 298,
981-987 (1978); E Heideman
Etc., German Chen Medical Witzsenshaftrich
Hikite, Vol. 107, pp. 695--697 (198
2); S. Levin, Islahel Journal Medi
Cal Sciences, Vol. 19, pp. 955-958 (1
983); A Billiau (above), F.B.G.
Nmberg and MW Harmon, J
・ A Armstrong (B.E.
W. Carter), "Interferon O
And its uses ", Springer Publishing, Berlin (198
4)]. Local treatment (intratumor, extratumor, intraventricular, intrafollicular,
3,0 only in intralesional, extralesional or intranasal administration)
00,000I. E. FIG. Lower doses are higher doses (above
The effect is almost the same as that of the systematic application described in the literature). In the case of an acute viral disease such as shingles,
500,000 I.D./kg body weight daily E. FIG. Α-I
FN or β-IFN is effective, that is,
About 30,000,000 I.D. E. FIG. [Tea
・ Sea Merigan (above); e.
Collology, Vol. 7, pp. 210-212 (198
4)]. For chronic viral diseases such as chronic active hepatitis B
In general, 3,000,000 to 10,000,000,
0I. E. FIG. Α-IFN or β-IFN daily or
Administer three times a week [E.M.
Rift Gastroenterology, Vol. 20, No. 105
-109 (1982); A. Billiau (above);
Su Levin (above)]. Based on in vitro experiments, γ-IFN was determined to be α-IFN.
Lower antiviral activity than IFN or β-IFN
[Eg A. Munoz, El Callas
Ko: FEMS / Microbiology Letters, 2
1, pp. 105-111 (1984)]. Based on these
Therefore, γ-IFN is conventionally used for systematic treatment of viral diseases.
Had not been used. Conventionally, patients with tumors are in the first phase
Was processed only within the range. Therefore, these diseases
Report on the therapeutic effect of γ-IFN on
Not [Es Yamazaki, Japanese Jana
Le Medical Science Biology, 37
Vol., Pp. 209-223 (1984);
Journal Biological Respect, Harwin et al.
Chib Modification, Volume 3, 559-607
(1984); Jay You Guttaman et al.
・ Research, Vol. 44, pp. 4164-4171 (19
84); Niederle et al. (H.
Chi Sienkens ed.), “Interferon biology”
(1984), Else Beer Publishing, Amsterdam (1
985)]. Conventionally, γ-IFN has been used for psoriasis, allergic diseases,
Used for Crohn's disease, amyotrophic lateral sclerosis and pain
Not. [0024] DETAILED DESCRIPTION OF THE INVENTION
In some clinical trials, patients with various diseases have been treated.
Was placed. To determine the optimal effective dose of γ-IFN
Once or many times a week at 50,000 I. E. FIG. -10
0,000,000I. E. FIG. Dose is systematically administered
Was. Surprisingly in these studies, γ-IFN
Unlike α-IFN or β-IFN, extremely many
The effective dose of γ-IFN is therapeutically effective for the disease
100,000-2,000,000 I.I. in all diseases E. FIG. ,
A very low dose in the range of 10-200 μg.
Was shown. Patients treated at such low doses
Γ- similar to the effect obtained at higher doses.
The effect of IFN was often confirmed. For high doses
The advantage of this extremely low dose is that it is particularly useful in two patients.
The therapeutic effect of γ-IFN was
As well as in patients withreferenceExample 1 and
2). The effect of γ-IFN at low doses was only
For example, adrenal gland tumor (referenceExamples 1-3), pseudomyxoma (referenceAn example
4), mammoma (referenceExample 5), immune cell tumor (referenceExample 6),
melanoma(referenceExample 7), Hodgkin's disease (referenceExample 8), Sumi
Nke tumor (referenceExample 9), Synovial sarcoma (referenceExample 10) and
Pancreatic cancer (referenceShown in various tumors as in Example 11)
Was. Particularly surprising effects are, for example, chronic activity
Hepatitis B (referenceExample 12), shingles (referenceExample 13 and
14) and Condylomata (referenceShown in Example 15)
Was. γ-IFN has been tested in these diseases
Α-IFN or β-IFN despite in vitro activity
Not only at the same dose as
Therapeutic effect even at doses much lower than Feron
Indicated. Similarly, in the following diseases, γ-IFN
The effect was shown: asthma (Example1), Crohn's disease (reference
Example 16), Amyotrophic lateral sclerosis (Reference Example 1)7) And pain
Pain (referenceExamples 1, 2, 3, 9 and 10). For systematic treatment, natural γ-IFN and
Recombinant γ-IFN can be administered as follows:
Times or minutes, hours, days or weeks
Intravenous, intramuscular and / or subcutaneous administration. tumor
Local for intra-, extra-tumoral, intra-lesional or extra-lesional administration
A systematic effect can be obtained as in the case of partial administration. All dosage forms
It is possible to use dosage forms known to the person skilled in the art.
For example, microcapsules and microcapsules,
It can be a ribosome and a plaster. Daily 1
00,000I. E. FIG. (Ie, about 10 μg) to 2,0
00,000I. E. FIG. (Ie, about 200 μg)
The dose can be administered once daily or divided into multiple doses
Can be administered. 0.1 for administration over several days
× 10⁶~ 2.0 × 10⁶I. E. FIG. (That is, about 10-2
00 μg) can be administered as follows: (A) Every day, (B) All for 2-6 days (C) Once a week (D) All for 2-4 weeks (E) Once a month (F) Each time the condition worsens. 0.1 × 10⁶~ 2.0 × 10⁶I. E. FIG. of
The dose is body weight 60 kg and body length 170 cm (body surface area)
1.74m^Two(Equivalent to)
Bore and Dubois, Arch, intern, M
ed, vol. 17, p. 863 (1916)]. Accordingly
For individual patients, the dose per individual is
Product 1m^Two0.06 × 10 per⁶~ 1.2 × 10⁶I.
E. FIG. Becomes To enhance the effect of γ-interferon preparation
Can further add the following substances: (A) by other interferons and / or leukocytes
Cell medium formed or produced by genetic engineering methods,
For example, IL1, IL2, CSF, MIF, MAF, T
Administration such as NF, LT and FGF; (B) tumors, viral diseases, psoriasis, allergic diseases and
Substances conventionally used to treat pain, such as
Agent, formate antagonist, prevention of metabolism of nucleic acid metabolism
Agent, spindle poison, antibiotic, immunotherapeutic, pyrimidine homolog
Body, purine nucleoside, amine, triazole nucleoside
Oside, corticoid, calcium, antihistamine,
Retinoid, photosensitive substance, lipoxygenase or
Fumaric acid, a chromoxygenase inhibitor
Salt, anesthetic, psychiatric, local anesthetic, antispasmodic, anti-lew
Gussets, calcium antagonists and beta blockers
Which administration. Detailed papers and others on this
Quality is Cliniché on by UICC (Hrsg.)
Cology, Springer Publishing (1982)
Pocket fish by J-Fisher (Hrsg.)
Check of Oncology, Urban and Schweiz
Listed in Emberberg (1983)
Biochemical Journal, Vol. 205, No.
Pages 1 to 13 (1982), and
Lancet by Luzon, Volume 2, 503-506
562-564, 617-621, 67
Pages 7 to 682, pages 736 to 739 (1984)
Dermatology by Brown-Falco et al.
-And-Benology, 3rd Edition, Springer
Edition, Berlin (1984)
On page 1-10 (1984)
Featured in Et J. Sen and A. Grouse
From Medwelt, Vol. 35, Nos. 1235-1240
P. (1984) and by MM Holey.
Engl, J.A. Med, 313, 84-95.
(1985). (C) For example, clinical oncology, springa
-Written by UICC (Hrsg.) In Publishing (1982)
Irradiation or introduction of radioactive material as listed
Radiation therapy. To prepare formulations for each dosage form, one skilled in the art
Auxiliaries known in the art, such as serum proteins (eg human blood
Albumin), buffer substances (for example, phosphate),
Sorbic acid, potassium sorbate, saturated vegetable fatty acids
Partial glyceride mixtures, water and salts or electrolysis
Quality, such as protamine sulfate, disodium phosphate, phosphorus
Dipotassium, sodium chloride and zinc salts are used
You. [0034] 【Example】<ReferenceExample 1> Patient: GS, male, 57 years old, weight 91 kg, height
182cm Diagnosis: Adrenal gland with bone relocation in right humerus, right arm
Intense pain and reduced motility Substance: Human γ-IFN preparation from E. coli Administration: intramuscular Treatment: 100 μg administered 4 times weekly for 2 weeks,
The dose was then increased to 200, 400, 800 and 1600.
increased to μg. Then 2100μ once a week for 4 weeks
g Result: Pain is clearly reduced after a single injection of 100 μg
A little and the patient can exercise the arm very well
Pain was no longer observed after 8 injections of 100 μg
Was not. Four days after a single injection of 2100 μg,
Pain occurred again in the upper arm. [0035]<ReferenceExample 2> Patient: eh, male, 51 years old, weighs 84 kg, body
182cm long Diagnosis: Adrenal gland with lung and bone metastases, pelvic area and
And lumbar-sacral area pain Substance: Human γ-IFN preparation from E. coli Administration: intramuscular Treatment: 100 μg administered 4 times weekly for 2 weeks,
Thereafter, increase the dose to 200 μg Result: Pain clearly reduced after two injections of 100 μg
Pain further decreased after 3 injections of 100 μg a little
did. After 4 injections of 200 μg, pain increased again
Was. [0036]<ReferenceExample 3> Patient: W. Male, 74 years old, weight 64k
g, height 170cm Diagnosis: Adrenal gland with transfer of skin, lungs and bones, xenogeneic vulgaris
Psoriasis Materials: human γ-IFN preparation from E. coli and diph
Fluoromethylornithine (DFMO) Administration method: γ-interferon is intravenous, DFMO is oral
Administration Therapeutic method: First, γ-IFN was applied at 50 μm daily for 10 days
g, then 100 μg daily for 7 days
And 3 × 4 g of DFMO was administered daily. Results: On day 7, pain decreased and on day 14
The patient was completely pain free. Psoriasis vulgaris after 12 days
Diminished and almost completely disappeared at the end of treatment. 17
Skin and liver metastases when patient is discharged after 1 day of treatment
Was partially reduced. General findings of patient clear
Was improved. [0038]<ReferenceExample 4> Patient: FD, male, 46 years old, weight 64 kg, body
183cm long Diagnosis: Peritoneal pseudomyxoma with four fistulas in the peritoneum Substance: Human γ-IFN preparation from E. coli Administration: intramuscular Treatment: 100 μg 4 times a week for 2 weeks Results: After 3 injections of 100 μg, of 4 fistomas
Two have disappeared. [0039]<ReferenceExample 5> Patient: KW, male, 59 years old, weight 73k
g, height 178cm Diagnosis: Diffuse bone marrow and liver involvement and excessive spinal enlargement
Malignant breast tumor with blood Substance: Human γ-IFN preparation from E. coli Administration: intravenous Treatment: 50 μg 5 times weekly for 5 weeks Results: After 5 weeks of treatment, the amount of enlarged liver was reduced and
And alkaline eluate from 1700E / 1 to 1000E / 1
Decrease in phosphatase (normal value is about 190E / 1)
Was observed. [0040]<ReferenceExample 6> Patient: YF, 54 years old Diagnosis: progressive polymorphic cell immunity Substance: Human γ-IFN preparation from E. coli Administration: intravenous Treatment: 50 μg 5 times weekly for 4 weeks Result: After two weeks of treatment, symptoms are no longer progressive
After another two weeks, lymph node swelling diminished. [0041]<ReferenceExample 7> Patient: eh, male Diagnosis: Fist-sized skin metastasis of melanoma, surgical removal of main tumor
did. Material: human γ-IFN from E. coli
Agent Administration: intravenous Treatment: 100 μg 3-5 times / week for 5 weeks Results: After 3 weeks of treatment, metastases were reduced by 90%, then
Stable. [0043]<ReferenceExample 8> Patient: GK, male, 50 years old, weight 85kg, height
172cm Diagnosis: Hodgkin's disease, stage IVb, liver, lung bone marrow and abdomen
Metastasis in lymph nodes Substance: Human γ-IFN preparation from human leukocytes Administration: subcutaneous administration, then intravenous administration Treatment: 0.01 x 10 daily for 3 weeks⁶Administration of
1.0 × 10⁶I. E. FIG. Increase to Results: A clear reduction in liver metastases at the end of treatment
Was. In addition, B-symptoms improved. [0044]<ReferenceExample 9> Patient: GP, male, 61 years old Diagnosis: Schminke tumor with recurrence of lung metastasis Substance: Human γ-IFN preparation from E. coli Administration: intravenous Treatment: 0.5x daily except Saturday for 12 weeks
10⁶I. E. FIG. RESULTS: Recurrence of lung metastases was delayed after 12 weeks of treatment
Partial healing was confirmed. The patient was released from the clinic. [0045]<ReferenceExample 10> Patient: BC, female, 36 years old, weight 52 kg Diagnosis: Pulmonary and pleural metastases and synovial meat with pleural infiltration
The tumor and the main tumor were removed by leg amputation. Substance: Human γ-IFN from E. coli
Agent Administration: intravenous Treatment: 50 μg daily Results: After 14 days of treatment, the pleural invasion disappeared. [0047]<ReferenceExample 11> Patient: HK, male, weight 86kg, height 181
cm Diagnosis: Pancreatic cancer with liver metastasis Substance: Human γ-IFN preparation from E. coli Administration: intravenous Treatment: 100 μg daily Results: From day 2, tumor pain was clearly reduced. Suffering
The subjects clearly reduced the need for strong anesthetics. [0048]<ReferenceExample 12> Patient: MK, female, 39 years old Diagnosis: chronic active hepatitis B Substance: Human γ-IFN preparation from E. coli Administration: intravenous Treatment: 100 μg daily Results: 5 × weekly for 10 weeks, 0.05 × dose
10⁶I. E. FIG. From 2.0 × 10⁶ I. E. FIG. Increased up to
I let you. Results: During treatment, DNAP was from 17422
It decreased to 5546. [0050]<ReferenceExample 13> Patient: ES, female Diagnosis: Herpes zoster with hearing impairment and facial paralysis Substance: Human γ-IFN preparation from leukocytes Administration: intramuscular Treatment: 0.5 × 10 twice daily for 5 days⁶I.
E. FIG. Result: Almost completely cured of shingles after 5 days of treatment
And the nerve function was normalized. [0051]<ReferenceExample 14> Patient: TS, male, 51 years old Diagnosis: Herpes zoster with facial paralysis Substance: Human γ-IFN preparation from E. coli Administration: intramuscular Treatment: 100 μg twice daily for 5 days Result: After 5 days of treatment, herpes zoster was almost cured, and
Nerve function was normalized. [0052]<ReferenceExample 15> Patient: N, female, 20 years old Diagnosis: Condyloma acuminatum Substance: Human γ-IFN preparation from E. coli Administration method: subcutaneous Treatment: 200 μg daily for 7 days Result: Condyloma almost completed within 3 weeks after the end of treatment
It has completely disappeared. [0053]<Example 1> Patient: IK, female, 56 years old Diagnosis: bronchial asthma Substance: Human γ-IFN preparation Administration method: subcutaneous Treatment: 100 μg each 3 times at 3 day intervals
Shooting Results: After treatment, the patient's asthma clearly decreased. Col
Drugs containing chicosteroids were no longer needed. Te
Administration of ophylline reduced the dose by half. [0054]<ReferenceExample 16> Patient: I-B, male, 44 years old, weighs 57 kg Diagnosis: Crohn's disease Substance: Human γ-IFN preparation from E. coli Administration: intramuscular or intravenous Treatment: 3-4 times weekly for 8 weeks, dose 0.0
2I. E. FIG. From 0.5 × 10⁶I. E. FIG. Increase until. Result: Clone index is 290 after treatment
To 59 (the Clone Index includes, for example, stool
Taking into account many factors such as frequency of abdominal pain, general findings, weight
Put in. This is evaluated with a score. Higher score
The more severe the symptoms). [0056]<Reference Example 17> Patient: W, male, age 61, weight 6
5kg, height 175cm Diagnosis: Amyotrophic lateral sclerosis Substance: Human γ-IFN preparation from E. coli Administration: intramuscular Treatment: 0.1 x 1 dose three times weekly for 4 weeks
0⁶I. E. FIG. From 1 × 10⁶I. E. FIG. Increase until. afterwards,
0.5 × 10 once a week for 4 weeks⁶I. E. FIG. . Result: During treatment, upper end function improved.
Was. Both hands can be bent and stretched again,
Some degree of extension and contraction and flexion of the elbow joint and slight
Rolling became possible. Lift the shoulder joint slightly again
Became possible. [0058] According to the present invention,Cures allergic diseases
Treatmentcan do.

──────────────────────────────────────────────────続 き Continued on the front page (31) Priority claim number 85111184.9 (32) Priority date September 4, 1985 (1985.9.4) (33) Priority claim country United Kingdom (GB) (72) Inventor Hans Joachim Oberbert Federal Republic of Germany, 7958 Laupheim, Adolf-Grebel-Strasse No. 12 (72) Inventor Josef Bruzoska Federal Republic of Germany, 7958 Laupheim, Hoppanbeek No. 10 (56) (JP, A) JP-A-59-130223 (JP, A) JP-A-59-98019 (JP, A) JP-A-59-51792 (JP, A) JP-A-58-103324 (JP, A) JP-A-58-159417 (JP, A) JP-A-55-98118 (JP, A) JP-A-58-90514 (JP, A) European Patent Application Publication 117470 (EP, A1) ( 58) Field surveyed (Int.Cl. ⁷ , DB name) A61K 38/21 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] A composition containing recombinant human [gamma] -interferon as an active ingredient and administered at intervals of days or months, comprising a composition for an adult patient having a body weight of about 60 kg and a body surface area of 1.7 m < ² >. The daily dose is 100,000-
A composition for systematically treating allergic diseases , defined to include 2 million International Standard Units. 2. The composition of claim 1, which is in a form suitable for intravenous, intramuscular, or subcutaneous administration.