WO2016139001A1 - New use of acetylsalicylic acid and derivatives thereof - Google Patents
New use of acetylsalicylic acid and derivatives thereof Download PDFInfo
- Publication number
- WO2016139001A1 WO2016139001A1 PCT/EP2016/000391 EP2016000391W WO2016139001A1 WO 2016139001 A1 WO2016139001 A1 WO 2016139001A1 EP 2016000391 W EP2016000391 W EP 2016000391W WO 2016139001 A1 WO2016139001 A1 WO 2016139001A1
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- Prior art keywords
- lysine
- natural
- acetylsalicylate
- acetylsalicylic acid
- pharmaceutical drugs
- Prior art date
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 16
- 241000700605 Viruses Species 0.000 claims abstract description 19
- 208000024891 symptom Diseases 0.000 claims abstract description 13
- 206010026749 Mania Diseases 0.000 claims abstract description 10
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 9
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 4
- 229940079593 drug Drugs 0.000 claims description 40
- JJBCTCGUOQYZHK-UHFFFAOYSA-N 2-acetyloxybenzoate;(5-amino-1-carboxypentyl)azanium Chemical compound OC(=O)C(N)CCCC[NH3+].CC(=O)OC1=CC=CC=C1C([O-])=O JJBCTCGUOQYZHK-UHFFFAOYSA-N 0.000 claims description 29
- JJBCTCGUOQYZHK-ZSCHJXSPSA-N 2-acetyloxybenzoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.CC(=O)OC1=CC=CC=C1C(O)=O JJBCTCGUOQYZHK-ZSCHJXSPSA-N 0.000 claims description 24
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- MGNBKNBEZGLHNF-UHFFFAOYSA-N (2-methylpyrazol-3-yl)boronic acid Chemical compound CN1N=CC=C1B(O)O MGNBKNBEZGLHNF-UHFFFAOYSA-N 0.000 claims description 23
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 20
- 235000015872 dietary supplement Nutrition 0.000 claims description 11
- 239000007853 buffer solution Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 241001430294 unidentified retrovirus Species 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims 2
- 208000022610 schizoaffective disease Diseases 0.000 claims 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 235000019766 L-Lysine Nutrition 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 229960003878 haloperidol Drugs 0.000 description 4
- 229960003646 lysine Drugs 0.000 description 4
- 206010012239 Delusion Diseases 0.000 description 3
- 108020004437 Endogenous Retroviruses Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 3
- 208000036752 Schizophrenia, paranoid type Diseases 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 229960004308 acetylcysteine Drugs 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 231100000868 delusion Toxicity 0.000 description 3
- 208000002851 paranoid schizophrenia Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical compound NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- -1 i.v. injection Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 150000002668 lysine derivatives Chemical class 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- 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
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
Definitions
- the present invention relates to a new use of acetylsalicylic acid and derivatives thereof or alternatively to acetylsalicylic acid and derivatives thereof for use in a hitherto unknown treatment of certain diseases or alternatively to a new method of treating certain diseases by administering acetylsalicylic acid and derivatives thereof.
- acetylsalicylic acid for combating or pain and fever.
- acetylsalicylic acid is useful for combating viruses, e.g. influenza viruses.
- DL-lysine-acetylsalicylate also known as DL-Lysine-2- acetoxybenzoate
- DL-lysine-acetylsalicylate also known as DL-Lysine-2- acetoxybenzoate
- the human genome encodes retroviruses (endogenous retroviruses) in a currently estimated proportion of about 7% of the genome. It is further known that under certain circumstances this information encoded in the genome can be read and lead to the complete expression of the corresponding retro virus(es). There have also been reports in the scientific literature that even the DNA of certain DNA-based virus(es) (for example some herpes simplex type(s)) may be incorporated into the human genome and under certain circumstances lead to the expression of the complete virus(es).
- retroviruses endogenous retroviruses
- endogenous (retro)viruses play a role in at least some diseases of the nervous system, in particular the central nervous system (CNS). e.g. in schizophrenia.
- CNS central nervous system
- acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate are useful for combating endogenous viruses, in particular endogenous retroviruses, and in particular in the nervous system, e.g. the central nervous system.
- acetylsalicylic acid the mixture thereof with DL-lysine hydrochloride or L- lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate (preferably in the presence of a weak base of a buffer system) are useful for combating the symptoms of at least certain types of depression, mania and paranoid psychosis or schizophrenia.
- the present invention relates to the use of acetylsalicylic acid, a mixture thereof with DL- lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L- lysine acetylsalicylate for combating an endogenous virus and/or symptoms caused by an endogenous virus; or acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate for use in combating an endogenous virus and/or symptoms caused by an endogenous virus; or a method of treatment for combating one or more of an endogenous virus and symptoms caused by an endogenous virus by administering safe and effective amount of one or more of acetylsalicylic acid, a mixture thereof with DL-
- the virus is preferably an endogenous retrovirus, and the symptoms are preferably depression, mania or paranoid psychosis.
- acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate are also contemplated for use in combating the symptoms of depression, mania and paranoid psychosis or schizophrenia.
- the present invention further relates a pharmaceutical composition
- a pharmaceutical composition comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
- the present invention also relates a pharmaceutical composition
- a pharmaceutical composition comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine
- hydrochloride and DL-lysine acetylsalicylate or L-lysine acetylsalicylate in the presence of a weak base or a buffer system.
- the invention relates to a kit of parts, comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL- lysine acetylsalicylate or L-lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
- “combating” means lowering (mitigating) or eliminating or preventing a virus titer or the symptoms accompanying the virus.
- Acetylsalicylic acid and DL-lysine-acetylsalicylate are well-known commercially available drugs and are on the market e.g. under the trade name Asprin® (Baser AG) and Apegic (Sanofi-Aventis), respectively.
- L-lysine-acetylsalicylate can be prepared in analogy to the well-known synthesis of DL-lysine-acetylsalicylate (se e.g. K.D. Rainsford: “Aspirin and Related Drugs", Taylor & Francis, London and New York, 2004) by substituting L-lysine for DL-lysine.
- the drugs of the inventive composition are administered in the presence of a pharmaceutically acceptable weak base, such as Na 2 C0 3 ' or in the presence of a pharmaceutically acceptable buffer system, such as Na H C0 3 /Na 2 C0 3 .
- a pharmaceutically acceptable weak base such as Na 2 C0 3 '
- a pharmaceutically acceptable buffer system such as Na H C0 3 /Na 2 C0 3 .
- compositions are preferably administered together with one or more natural pharmaceutical drugs or remedies having antiviral and immune-supporting effects, such as Succus liquiritiae, and/or other pharmaceutical drugs having immune-supporting effects, such as e.g. acetylcysteine as a sulfur source, and/or nutritional supplements having positive effects on the immune system, such as Zink, Vitamin D, Vitamin B3, Vitamin B6 and Vitamin B12.
- natural pharmaceutical drugs or remedies having antiviral and immune-supporting effects such as Succus liquiritiae
- other pharmaceutical drugs having immune-supporting effects such as e.g. acetylcysteine as a sulfur source
- nutritional supplements having positive effects on the immune system, such as Zink, Vitamin D, Vitamin B3, Vitamin B6 and Vitamin B12.
- the dosage of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L- lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate fro combating an acute disease generally corresponds to 1 - 3 g acetylsalicylic acid, optionally present in the lysine derivative. Usually, this dosage is administered for about 2 to about 6 days.
- a prophylactic dosage may be lower, such as 100 mg to 1 g, based on acetylsalicylic acid.
- the above-mentioned drugs for use according of the invention are usually administered in combination with at least one carrier. Any further pharmaceutically acceptable excipients, such as fillers, lubricants, flavors etc. may be included
- the dosage forms thereof may take any pharmaceutical dosage form known for this class of drugs, i.e. solid acids or salts, e.g. the form of tablets, capsules, lozenges, dosage forms in a liquid carrier for ingestions or injection, e.g. i.v. injection, suppositories and solid or dosage liquid dosage forms with retarded or prolonged action.
- Such dosage forms are well-known to the person skilled in the art; see e.g. Remington, The Science and Practice of Pharmacy, Ed. Allen, Loyd V. Jr., 21nd Edition, 2012. This also applies to the pharmaceutical compositions of the present invention.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to acetylsalicylic acid and derivatives thereof for use in treating symptoms caused by endogenous virus, i.e. depression, schizophrenia, mania or psychosis.
Description
New Use of Acetylsalicylic Acid and Derivatives Thereof Filed of the Invention The present invention relates to a new use of acetylsalicylic acid and derivatives thereof or alternatively to acetylsalicylic acid and derivatives thereof for use in a hitherto unknown treatment of certain diseases or alternatively to a new method of treating certain diseases by administering acetylsalicylic acid and derivatives thereof. Background of the Invention
It is known to use acetylsalicylic acid for combating or pain and fever. There are also reports in the scientific literature that acetylsalicylic acid is useful for combating viruses, e.g. influenza viruses. DL-lysine-acetylsalicylate (also known as DL-Lysine-2- acetoxybenzoate) is also used for combating pain and fever.
It is further known to the person skilled in the art that the human genome encodes retroviruses (endogenous retroviruses) in a currently estimated proportion of about 7% of the genome. It is further known that under certain circumstances this information encoded in the genome can be read and lead to the complete expression of the corresponding retro virus(es). There have also been reports in the scientific literature that even the DNA of certain DNA-based virus(es) (for example some herpes simplex type(s)) may be incorporated into the human genome and under certain circumstances lead to the expression of the complete virus(es).
Furthermore, there are indications in the scientific literature that endogenous (retro)viruses play a role in at least some diseases of the nervous system, in particular the central nervous system (CNS). e.g. in schizophrenia. It has now surprisingly found that acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate (preferably in the presence of a weak base of a buffer system) are useful for combating endogenous viruses, in particular endogenous retroviruses, and in particular
in the nervous system, e.g. the central nervous system. Furthermore, it was surprisingly found that acetylsalicylic acid, the mixture thereof with DL-lysine hydrochloride or L- lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate (preferably in the presence of a weak base of a buffer system) are useful for combating the symptoms of at least certain types of depression, mania and paranoid psychosis or schizophrenia.
Summary of the Invention The present invention relates to the use of acetylsalicylic acid, a mixture thereof with DL- lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L- lysine acetylsalicylate for combating an endogenous virus and/or symptoms caused by an endogenous virus; or acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate for use in combating an endogenous virus and/or symptoms caused by an endogenous virus; or a method of treatment for combating one or more of an endogenous virus and symptoms caused by an endogenous virus by administering safe and effective amount of one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L- lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate.
The virus is preferably an endogenous retrovirus, and the symptoms are preferably depression, mania or paranoid psychosis. Thus, acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride as well as DL-lysine acetylsalicylate or L-lysine acetylsalicylate are also contemplated for use in combating the symptoms of depression, mania and paranoid psychosis or schizophrenia.
The present invention further relates a pharmaceutical composition comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural
pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
The present invention also relates a pharmaceutical composition comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine
hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate in the presence of a weak base or a buffer system.
Finally, the invention relates to a kit of parts, comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL- lysine acetylsalicylate or L-lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
Detailed Description In the context of the present invention, "combating" means lowering (mitigating) or eliminating or preventing a virus titer or the symptoms accompanying the virus.
It was surprisingly found in the present invention that the symptoms of depression, mania and paranoid psychosis or schizophrenia can successfully combated with one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine
hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate. From the findings of the scientific literature it may be concluded that endogenous retroviruses play a major role in the etiology of the above-mentioned diseases. It must be concluded that acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine
hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate combat these viruses, since it is not known that those drugs have a major impact on the neurotransmitters or the receptors thereof which also play a major role in the etiology of the above- mentioned diseases.
Acetylsalicylic acid and DL-lysine-acetylsalicylate (DL-Lysine-2-acetoxybenzoate) are well-known commercially available drugs and are on the market e.g. under the trade name Asprin® (Baser AG) and Apegic (Sanofi-Aventis), respectively. L-lysine-acetylsalicylate can be prepared in analogy to the well-known synthesis of DL-lysine-acetylsalicylate (se e.g. K.D. Rainsford: "Aspirin and Related Drugs", Taylor & Francis, London and New York, 2004) by substituting L-lysine for DL-lysine.
Preferably the drugs of the inventive composition are administered in the presence of a pharmaceutically acceptable weak base, such as Na2C03' or in the presence of a pharmaceutically acceptable buffer system, such as NaHC03/Na2C03.
Furthermore, they are preferably administered together with one or more natural pharmaceutical drugs or remedies having antiviral and immune-supporting effects, such as Succus liquiritiae, and/or other pharmaceutical drugs having immune-supporting effects, such as e.g. acetylcysteine as a sulfur source, and/or nutritional supplements having positive effects on the immune system, such as Zink, Vitamin D, Vitamin B3, Vitamin B6 and Vitamin B12. The dosage of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L- lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate fro combating an acute disease generally corresponds to 1 - 3 g acetylsalicylic acid, optionally present in the lysine derivative. Usually, this dosage is administered for about 2 to about 6 days. A prophylactic dosage may be lower, such as 100 mg to 1 g, based on acetylsalicylic acid.
The above-mentioned drugs for use according of the invention are usually administered in combination with at least one carrier. Any further pharmaceutically acceptable excipients, such as fillers, lubricants, flavors etc. may be included The dosage forms thereof may take any pharmaceutical dosage form known for this class of drugs, i.e. solid acids or salts, e.g. the form of tablets, capsules, lozenges, dosage forms in a liquid carrier for ingestions or injection, e.g. i.v. injection, suppositories and solid or dosage liquid dosage forms with retarded or prolonged action. Such dosage forms are well-known to the person skilled in
the art; see e.g. Remington, The Science and Practice of Pharmacy, Ed. Allen, Loyd V. Jr., 21nd Edition, 2012. This also applies to the pharmaceutical compositions of the present invention.
Examples
Example 1
A 46 years old female patient has been suffering from a depression characterized among others by a mild stupor presumably because of a very low dopamine level for three days. She had not seen a physician because of lack of time, since her work progressed very slowly. On day 4 her condition improved considerably within one hour after having taken DL-lysine acetylsalicylate corresponding to 1000 mg acetylsalicylic acid. After two further ingestions of the same dosage 5 hours later and on the next day, she felt completely recovered.
Example 2
A 57 years old male patient had been treated in a psychiatric hospital among others with high doses of haloperidol because of an acute paranoid psychosis. After abating of his delusions he was dismissed with the recommendation to take 5 mg haloperidol per day, among others. Although he had not longer any delusions, the patient did not feel well. 4 days after his dismissal he started to take DL-lysine acetylsalicylate corresponding to 1000 mg acetylsalicylic acid three times per day, together with a table spoon of Succus liquiritiae per day, a zinc salt corresponding to 60 mg zinc per day and acetylcysteine in a dosage of 1,200 mg per day. After three days he was free of any ailments.
Example 3
A 66 years old female patient who had been suffering for many years of recurrent schizoaffective psychoses felt the signs of the beginning of a mania. She went to a psychiatric hospital for treatment and was administered 2 mg haloperidol per day. After 4 days, she began to take DL-lysine acetylsalicylate corresponding to 1000 mg
acetylsalicylic acid one to two times per day without knowledge of the staff of the hospital.
Later on she also took 1 table spoon of Succus liquiritiae as well as zinc and
acetylcysteine. She then refused to take any further haloperidol except for once in the evening when she was sleepless. The condition of the patient improved, the mania became less and she did not develop any delusions which she usually did after the mania. After two weeks she was able to work part time again in a demanding job.
All patent applications and patents, literature articles and books cited in this speicification are incorporated in their entirety herein by reference.
Claims
1. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use in combating an endogenous virus and/or symptoms caused by an endogenous virus.
2. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to claim 1 , wherein the use is effected in the presence of a pharmaceutically acceptable weak base or buffer system.
3. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to claim 1 or 2, wherein the use is effected in the presence of one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
4. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to any of claims 1 to 3, wherein the endogenous virus is an endogenous retrovirus.
5. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to any of claims 1 to 4, wherein the symptoms are the symptoms of depression, paranoid psychosis, schizophrenia, schizoaffective psychosis, mania or manic-depressive disorder.
6. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to any of claims 1 to 5, wherein the dosage in the use is a drug dosage corresponding 1 to 3 mg acetylsalicylic acid per day.
7. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use according to any of claims 1 to 5, wherein the drug dosage corresponding 1 to 3 mg acetylsalicylic acid per day is administered for 2 to 6 days.
8. Acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride, DL-lysine acetylsalicylate and/or L-lysine acetylsalicylate for use in treating symptoms of depression, paranoid psychosis, schizophrenia, schizoaffective psychosis, mania or manic-depressive disorder.
9. Pharmaceutical composition, comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
10. Pharmaceutical composition, comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL-lysine acetylsalicylate or L-lysine acetylsalicylate and a pharmaceutically acceptable .weak base or a buffer system
10. Kit of parts, comprising one or more of acetylsalicylic acid, a mixture thereof with DL-lysine hydrochloride or L-lysine hydrochloride; and DL-lysine acetylsalicylate or L- lysine acetylsalicylate, preferably in the presence of a weak base or a buffer system and one or more natural pharmaceutical drugs or natural remedies; or one or more natural pharmaceutical drugs or natural remedies and one or more food supplements; or one or more natural pharmaceutical drugs or natural remedies and one or more further
pharmaceutical drugs; or one or more natural pharmaceutical drugs or natural remedies, one or more food supplements and one or more further pharmaceutical drugs.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16712205.0A EP3265076A1 (en) | 2015-03-04 | 2016-03-04 | New use of acetylsalicylic acid and derivatives thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102015002709.3 | 2015-03-04 | ||
| DE102015002709.3A DE102015002709A1 (en) | 2015-03-04 | 2015-03-04 | New use of acetylsalicylic acid and a derivative thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016139001A1 true WO2016139001A1 (en) | 2016-09-09 |
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ID=55640663
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2016/000391 WO2016139001A1 (en) | 2015-03-04 | 2016-03-04 | New use of acetylsalicylic acid and derivatives thereof |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3265076A1 (en) |
| DE (1) | DE102015002709A1 (en) |
| WO (1) | WO2016139001A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11911400B1 (en) | 2017-05-30 | 2024-02-27 | Rhoshan Pharmaceuticals, Inc. | In-vial deposition of a stable, sterile and crystalline O-acetyl salicylic acid (aspirin) |
| US12048708B2 (en) | 2021-08-19 | 2024-07-30 | Rhoshan Pharmaceuticals, Inc. | In-vial deposition of a stable, sterile and crystalline o-acetyl salicylic acid (aspirin) |
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| JPS62265227A (en) * | 1986-05-13 | 1987-11-18 | Green Cross Corp:The | Preventing and treating agent for medicinal peripheral neuropathy |
| JPH08291074A (en) * | 1995-04-14 | 1996-11-05 | Synthelabo Sa | Combined substance of dl-lysine acetyl-salicylate and vitamin e |
| EP1378236A1 (en) * | 2001-03-23 | 2004-01-07 | Ajinomoto Co., Inc. | Agents against stress-induced diseases drugs |
| KR101302119B1 (en) * | 2013-02-28 | 2013-08-30 | 김돈규 | Manufacturing method of functional liquid for enhancing nutrients absorption rate, and functional liquid manufactured by the same |
| US20140066413A1 (en) * | 2011-06-13 | 2014-03-06 | Aspir-Tek, Inc. | Analgesic composition and method of making the same |
-
2015
- 2015-03-04 DE DE102015002709.3A patent/DE102015002709A1/en not_active Withdrawn
-
2016
- 2016-03-04 WO PCT/EP2016/000391 patent/WO2016139001A1/en unknown
- 2016-03-04 EP EP16712205.0A patent/EP3265076A1/en not_active Withdrawn
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|---|---|---|---|---|
| JPS62265227A (en) * | 1986-05-13 | 1987-11-18 | Green Cross Corp:The | Preventing and treating agent for medicinal peripheral neuropathy |
| JPH08291074A (en) * | 1995-04-14 | 1996-11-05 | Synthelabo Sa | Combined substance of dl-lysine acetyl-salicylate and vitamin e |
| EP1378236A1 (en) * | 2001-03-23 | 2004-01-07 | Ajinomoto Co., Inc. | Agents against stress-induced diseases drugs |
| US20140066413A1 (en) * | 2011-06-13 | 2014-03-06 | Aspir-Tek, Inc. | Analgesic composition and method of making the same |
| KR101302119B1 (en) * | 2013-02-28 | 2013-08-30 | 김돈규 | Manufacturing method of functional liquid for enhancing nutrients absorption rate, and functional liquid manufactured by the same |
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| Title |
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| CAPONE ET AL: "P2.28:Acetylsalicylic acid accelerates the antidepressant effect of fluoxetine in a rat model of depression", EUROPEAN NEUROPSYCHOPHARMACOLOGY, ELSEVIER SCIENCE PUBLISHERS BV, AMSTERDAM, NL, vol. 16, 1 January 2006 (2006-01-01), pages S61, XP005353450, ISSN: 0924-977X, DOI: 10.1016/S0924-977X(06)80074-X * |
| DATABASE WPI Week 201378, Derwent World Patents Index; AN 2013-N37489, XP002758726 * |
| VIJAYANAND ARLALIMATH ET AL: "ENHANCEMENT OF ANTI- INFLAMMATORY ACTIVITY OF ASPIRIN BY ZINC", 1 January 2008 (2008-01-01), pages 51 - 60, XP055280306, Retrieved from the Internet <URL:http://pharmacologyonline.silae.it/files/archives/2008/vol2/05_Vivek.pdf> [retrieved on 20160614] * |
| YOLKEN ROBERT: "Viruses and schizophrenia: a focus on herpes simplex virus.", HERPES : THE JOURNAL OF THE IHMF, vol. 11 Suppl 2, 1 June 2004 (2004-06-01), pages 83A - 88A, XP009190392 * |
| ZEINODDINI ATEFEH ET AL: "l-lysine as an adjunct to risperidone in patients with chronic schizophrenia: A double-blind, placebo-controlled, randomized trial", JOURNAL OF PSYCHIATRIC RESEARCH, vol. 59, 1 December 2014 (2014-12-01), pages 125 - 131, XP029079002, ISSN: 0022-3956, DOI: 10.1016/J.JPSYCHIRES.2014.08.016 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11911400B1 (en) | 2017-05-30 | 2024-02-27 | Rhoshan Pharmaceuticals, Inc. | In-vial deposition of a stable, sterile and crystalline O-acetyl salicylic acid (aspirin) |
| US12048708B2 (en) | 2021-08-19 | 2024-07-30 | Rhoshan Pharmaceuticals, Inc. | In-vial deposition of a stable, sterile and crystalline o-acetyl salicylic acid (aspirin) |
Also Published As
| Publication number | Publication date |
|---|---|
| DE102015002709A1 (en) | 2016-09-08 |
| EP3265076A1 (en) | 2018-01-10 |
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