DE4122784A1 - Drug compsn. for treatment of HIV - contains immunoglobulin and sulphide cpd., which act synergistically on reticuloendothelial system - Google Patents
Drug compsn. for treatment of HIV - contains immunoglobulin and sulphide cpd., which act synergistically on reticuloendothelial systemInfo
- Publication number
- DE4122784A1 DE4122784A1 DE19914122784 DE4122784A DE4122784A1 DE 4122784 A1 DE4122784 A1 DE 4122784A1 DE 19914122784 DE19914122784 DE 19914122784 DE 4122784 A DE4122784 A DE 4122784A DE 4122784 A1 DE4122784 A1 DE 4122784A1
- Authority
- DE
- Germany
- Prior art keywords
- igg
- pharmaceutical composition
- treatment
- immunoglobulins
- hiv infections
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 14
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 14
- 210000000865 mononuclear phagocyte system Anatomy 0.000 title claims abstract description 4
- 239000003814 drug Substances 0.000 title claims description 7
- 229940079593 drug Drugs 0.000 title claims description 4
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 title abstract 3
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 16
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 12
- 229940072221 immunoglobulins Drugs 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 7
- 108010024636 Glutathione Proteins 0.000 claims abstract description 6
- 229960003180 glutathione Drugs 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000101 thioether group Chemical group 0.000 claims description 6
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 5
- 229960004308 acetylcysteine Drugs 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 2
- 150000001944 cysteine derivatives Chemical class 0.000 claims 1
- 210000004698 lymphocyte Anatomy 0.000 abstract description 10
- 239000000443 aerosol Substances 0.000 abstract description 2
- 230000005923 long-lasting effect Effects 0.000 abstract description 2
- 210000002540 macrophage Anatomy 0.000 abstract description 2
- 210000001616 monocyte Anatomy 0.000 abstract description 2
- 239000012050 conventional carrier Substances 0.000 abstract 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 abstract 1
- 235000018417 cysteine Nutrition 0.000 abstract 1
- 208000030507 AIDS Diseases 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 241000700605 Viruses Species 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- IOEJYZSZYUROLN-UHFFFAOYSA-M Sodium diethyldithiocarbamate Chemical compound [Na+].CCN(CC)C([S-])=S IOEJYZSZYUROLN-UHFFFAOYSA-M 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39516—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum from serum, plasma
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Gegenstand der vorliegenden Erfindung ist eine pharma zeutische Zusammensetzung zur Behandlung von HIV-Infektio nen sowie die Verwendung der pharmazeutischen Zusammen setzung zur Herstellung eines Arzneimittels zur Behandlung von HIV-Infektionen, zur Aktivierung des retikulo-endo thelialen Systems und zur dauerhaften Einstellung des T4/T8-Verhältnisses bei HIV-Infektionen.The present invention relates to a pharmaceutical composition for the treatment of HIV infections and the use of the pharmaceutical composition for the manufacture of a medicament for the treatment of HIV infections, for the activation of the reticulo-endothelial system and for the permanent adjustment of the T 4 / T 8 ratio in HIV infections.
Die zur Zeit gängigen AIDS-Therapien basieren u. a. auf der Applikation von Hemmstoffen der reversen Transkrip tase. Dieses Enzym ist verantwortlich für die Umschreibung der viralen Ribonukleinsäure (RNA) des HIV-Virus in DNA. Als besonders wirksam haben sich bestimmte Di-desoxy nucleoside herausgestellt, zum Beispiel 3′-Azido-2′,3′- di-desoxytymidin (AZT). Diese Medikamente besitzen jedoch ebenfalls nicht unerhebliche Nebenwirkungen. Eine voll ständige Genesung von einer HIV-Infektion wurde auch bei Applikation von AZT nicht berichtet. Eine Übersichtsar beit findet sich in AIDS Treatment Registry Inc., August bis September 1990, New York.The current AIDS therapies are based u. a. on the application of inhibitors to the reverse transcript tase. This enzyme is responsible for the description the viral ribonucleic acid (RNA) of the HIV virus in DNA. Certain di-deoxy have proven particularly effective highlighted nucleosides, for example 3′-azido-2 ′, 3′- di-deoxytymidine (AZT). However, these drugs do also not insignificant side effects. A full one constant recovery from HIV infection has also been reported Application of AZT not reported. An overview beit can be found in AIDS Treatment Registry Inc., August until September 1990, New York.
Die DE-OS 39 40 784 beschreibt ein Verfahren und einen Kit zur Behandlung von AIDS, bei dem Antikörper gegen die reverse Transkriptase des HIV verabreicht werden. Dabei wird im Sinne einer passiven Immuntherapie τ-Globulin von Patienten, von denen bekannt ist, daß sie hohe Antikör per-Titer gegen die reverse Transkriptase haben, oder entsprechende monoklonale Antikörper verwendet.DE-OS 39 40 784 describes a method and a Kit for the treatment of AIDS, in which antibodies against the reverse transcriptase of HIV can be administered. Here is used in the sense of passive immunotherapy τ-globulin Patients known to have high levels of antibody have per-titer against reverse transcriptase, or appropriate monoclonal antibodies are used.
Andere Therapieansätze gehen in die Richtung, daß Anker protein, mit dem das Virus an die zu infizierende Primär zelle andockt, zum Beispiel durch Antikörper, zu maskie ren. Auf diese Weise soll ein Eindringen des Virus in die Zelle verhindert werden. Ausgangspunkt dafür sind tie rische monoklonale Antikörper, die gegen bestimmte Glyco proteine der viralen Oberfläche gerichtet sind. Auch diese Therapieansätze stecken noch in den Anfängen.Other therapeutic approaches go in the direction of anchors protein with which the virus attaches to the primary to be infected cell docks, for example by antibodies, to maskie In this way, the virus should penetrate the Cell can be prevented. The starting point for this are tie monoclonal antibodies against certain glyco proteins are directed to the viral surface. This too Therapeutic approaches are still in the early stages.
Roederer, M., et al., Proc. Natl. Acad. Sci. USA, Vol. 87, S. 4884-4888 (1990), berichten, daß mit N-acetyl- 1-cystein die Stimulation von HIV ausgelöst durch Tumor nekrosefaktor α und Phorbol-12-myristat-13-acetat ver hindert werden kann. Die Autoren schließen daraus, daß die Menge der HIV-Produktion durch intrazelluläre Thiol spiegel beeinflußt werden kann.Roederer, M., et al., Proc. Natl. Acad. Sci. USA, Vol. 87, pp. 4884-4888 (1990) report that with N-acetyl- 1-cysteine stimulation of HIV triggered by tumor necrosis factor α and phorbol-12-myristat-13-acetate ver can be prevented. The authors conclude that the amount of HIV production by intracellular thiol mirror can be influenced.
Lang, J.-M., et al. berichten in The Lancet, Deutsche Ausgabe, Nr. 12, Seiten 803 ff. (1988), über eine Be handlung von HIV-Infektionen mit Dithiocarbnatrium (Immuthiol). Die Autoren stellten bei Gabe von Dithiocarb die Verhinderung der Progredienz der AIDS-Erkrankung im Vergleich zu einer Kontrollgruppe fest. Darüber hinaus verbesserte sich die Symptomatik des klinischen Status und der Immunfunktion in signifikanter Weise. Untersucht wurden als Parameter die Symptomatik und die CD4⁺-Zell zahlen. Die Autoren führen die Effekte auf allgemeine cytoprotektive Eigenschaften des Immunthiol aufgrund des Einfangens freier Sauerstoffradikale und Beeinflussung des Glutathionstoffwechsels zurück. Sie stellten fest, daß die CD4⁺-Zellzahl anstieg und keine Verschlechterung des Zustands eintrat. Lang, J.-M., et al. report in The Lancet, German Edition, No. 12, pages 803 ff. (1988), about a Be treatment of HIV infections with dithiocarb sodium (Immuthiol). The authors provided dithiocarb the prevention of the progression of AIDS in the Comparison to a control group. Furthermore the symptoms of clinical status improved and immune function in a significant way. Examined the symptoms and the CD4⁺ cell were used as parameters numbers. The authors attribute the effects to general cytoprotective properties of the immunthiol due to the Trapping free oxygen radicals and influencing of glutathione metabolism. They found that the CD4⁺ cell count increased and no deterioration of the state occurred.
Überraschenderweise wurde nun gefunden, daß durch Verab reichung von Immunoglobulinen in Kombination mit organisch gebundenen Sulfidgruppen eine Behandlung von HIV-In fektionen möglich ist.Surprisingly, it has now been found that by Ad administration of immunoglobulins in combination with organic bound sulfide groups a treatment for HIV-In fections is possible.
Gegenstand der vorliegenden Erfindung ist somit aber eine pharmazeutische Zusammensetzung gemäß den Merkmalen des Anspruchs l.However, the subject of the present invention is a pharmaceutical composition according to the characteristics of Claim l.
Vorzugsweise besteht die Immunoglobulinfraktion aus Immunoglobulin des IgG-, IgA-, IgM- und/oder IgD-Typs. Besonders bevorzugt sind die IgG-Unterklassen 1 bis 4, insbesondere die IgG 2a- und/oder IgG 2b-Unterklassen.The immunoglobulin fraction preferably consists of Immunoglobulin of the IgG, IgA, IgM and / or IgD type. The IgG subclasses 1 to 4 are particularly preferred, in particular the IgG 2a and / or IgG 2b subclasses.
Als niedermolekulare Substanz mit mindestens einer or ganisch gebundenen Sulfidgruppe kommen insbesondere Glutathion oder ein N-Acylcysteinderivat in Frage. Ganz besonders bevorzugt ist N-Acetyl-L-cystein.As a low molecular weight substance with at least one or ganically bound sulfide group come in particular Glutathione or an N-acylcysteine derivative. All N-acetyl-L-cysteine is particularly preferred.
Bevor die Behandlung mit der Wirkstoffkombination aus Immunoglobulin und der niedermolekularen, mindestens eine organische Sulfidgruppe aufweisenden Verbindung einsetzt, kann der zu behandelnde Patient mit Immunoglobulinen für einen bestimmten Zeitraum vorbehandelt werden. Dieser Zeitraum kann bis zu mehreren Monaten betragen. Danach kann der Patient dann mit dem erfindungsgemäßen Mittel behandelt werden.Before treatment with the active ingredient combination Immunoglobulin and low molecular weight, at least one uses a compound having an organic sulfide group, can the patient to be treated with immunoglobulins for be pretreated for a certain period of time. This The period can be up to several months. After that the patient can then use the agent according to the invention be treated.
Als Indikator für das Fortschreiten einer AIDS-Infektion ist allgemein das Verhältnis der T4-Lymphozyten zu den T8-Lymphozyten anerkannt. Die Fig. 1 zeigt den Verlauf der T4-Zellpopulation bei einem Patienten, der sero positiv auf eine HIV-Infektion ist.The ratio of T 4 lymphocytes to T 8 lymphocytes is generally recognized as an indicator of the progression of AIDS infection. Fig. 1 shows the course of T cell population in a patient 4, the positive HIV-infection is a sero.
Die Fig. 2 zeigt den Verlauf der T8-Zellpopulation bei demselben Patienten. Fig. 2 shows the course of T 8 cell population in the same patient.
Es ist deutlich zu erkennen, daß nach einmaliger Verab reichung von N-Acetyl-L-cystein zunächst der T4-Lympho zytengehalt stark ansteigt. Zeitlich versetzt steigt auch der T8-Lymphozytengehalt. Nach einem Absinken der Lympho zytenzahl stabilisiert sich die absolute Zahl der Lympho zyten auf einem höheren Niveau als vor der Stimulation. Eine zweite Gabe von N-Acetylcystein bewirkt ein erneutes anhaltendes Ansteigen der beiden Lymphozytenpopulationen. Dieser lang andauernde Effekt (6 bis 8 Wochen) ist be merkenswert, da die Halbwertzeit von Glutathion beim Menschen in vivo ungefähr 1,6 Minuten beträgt bei einer einmaligen intravenös verabreichten Dosis Glutathion von 1,56 mg pro Kilogramm Körpergewicht (Wendel, A. und Cikryt, P., FEBS Letters 120, 209-211 (1980)). Die Ver mutung, daß nach der Stimulation Viren nachgewiesen wer den könnten, in der vermehrten Subpopulation der Leuko zyten, hat sich nicht bestätigt (Fig. 1 an den mit x markierten Positionen). Die erfindungsgemäße pharma zeutische Zusammensetzung ist somit zur Behandlung von HIV-Infektionen geeignet.It can be clearly seen that after a single administration of N-acetyl-L-cysteine, the T 4 lymphocyte content initially rises sharply. The T 8 lymphocyte content also increases at different times. After a decrease in the number of lymphocytes, the absolute number of lymphocytes stabilizes at a higher level than before the stimulation. A second dose of N-acetylcysteine causes the two lymphocyte populations to increase again. This long-lasting effect (6 to 8 weeks) is remarkable since the half-life of glutathione in humans in vivo is approximately 1.6 minutes with a single intravenous dose of glutathione of 1.56 mg per kg body weight (Wendel, A. and Cikryt, P., FEBS Letters 120, 209-211 (1980)). The assumption that viruses could be detected after stimulation in the increased subpopulation of leukocytes has not been confirmed ( FIG. 1 at the positions marked with x). The pharmaceutical composition according to the invention is thus suitable for the treatment of HIV infections.
Die erfindungsgemäße pharmazeutische Zubereitung ist ge eignet zur Herstellung eines Arzneimittels zur Behandlung von HIV-Infektionen. Darüber hinaus ist die erfindungsge mäße pharmazeutische Zusammenstellung auch geeignet zur Herstellung eines Mittels zur Aktivierung des retikulo endothelialen Systems, aus dem die Lymphozyten, Monozyten und Makrophagen hervorgehen.The pharmaceutical preparation according to the invention is ge is suitable for the manufacture of a medicament for treatment of HIV infections. In addition, the fiction moderate pharmaceutical composition also suitable for Production of a means for activating the retikulo endothelial system from which the lymphocytes, monocytes and macrophages emerge.
Die erfindungsgemäße pharmazeutische Zusammensetzung ist geeignet zur Herstellung eines Arzneimittels zur dauer haften Einstellung des T4/T8-Lymphozytenverhältnisses bei HIV-Infektionen.The pharmaceutical composition according to the invention is suitable for the manufacture of a medicament for the permanent adjustment of the T 4 / T 8 lymphocyte ratio in HIV infections.
Die erfindungsgemäße pharmazeutische Zusammensetzung wird vorzugsweise intramuskulär oder intravenös verabreicht. The pharmaceutical composition according to the invention is preferably administered intramuscularly or intravenously.
Jedoch sind auch Verabreichungen in Form eines Aerosols, intrarectal, oral und auch topikale Anwendungen möglich.However, administration in the form of an aerosol, intrarectal, oral and also topical applications possible.
Die erfindungsgemäße pharmazeutische Zusammensetzung be wirkt einen immunomodulatorischen Effekt provoziert durch die synergistische Aktion eines Arzneimittels entstehend aus einem Gemisch von Immunoglobulinen vom Tpy IgG, IgA, IgM oder IgD von nicht HIV-infizierten Patienten und N- Acetylcystein für die Behandlung der asymptomatischen und symptomatischen Phase von HIV-Infektionen, mittels intra muskulärer, intravenöser, oraler, rectaler, topikaler und/oder bronchialer Anwendung.The pharmaceutical composition according to the invention be acts provoked by an immunomodulatory effect the synergistic action of a drug arises from a mixture of immunoglobulins from Tpy IgG, IgA, IgM or IgD from non-HIV infected patients and N- Acetylcysteine for the treatment of asymptomatic and symptomatic phase of HIV infections, by means of intra muscular, intravenous, oral, rectal, topical and / or bronchial application.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19914122784 DE4122784A1 (en) | 1991-07-10 | 1991-07-10 | Drug compsn. for treatment of HIV - contains immunoglobulin and sulphide cpd., which act synergistically on reticuloendothelial system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19914122784 DE4122784A1 (en) | 1991-07-10 | 1991-07-10 | Drug compsn. for treatment of HIV - contains immunoglobulin and sulphide cpd., which act synergistically on reticuloendothelial system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE4122784A1 true DE4122784A1 (en) | 1993-01-14 |
Family
ID=6435806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19914122784 Withdrawn DE4122784A1 (en) | 1991-07-10 | 1991-07-10 | Drug compsn. for treatment of HIV - contains immunoglobulin and sulphide cpd., which act synergistically on reticuloendothelial system |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE4122784A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6932967B2 (en) | 2001-03-22 | 2005-08-23 | Michael R. Simon | Human medical treatment by aerosol inhalation of immunoglobulin A |
-
1991
- 1991-07-10 DE DE19914122784 patent/DE4122784A1/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6932967B2 (en) | 2001-03-22 | 2005-08-23 | Michael R. Simon | Human medical treatment by aerosol inhalation of immunoglobulin A |
| US6967106B2 (en) | 2001-03-22 | 2005-11-22 | Simon Michael R | Human medical treatment by aerosol inhalation of immunoglobulin A |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |