US3622666A - Methods for treating bacterial infections with phrenosin - Google Patents
Methods for treating bacterial infections with phrenosin Download PDFInfo
- Publication number
- US3622666A US3622666A US709937A US3622666DA US3622666A US 3622666 A US3622666 A US 3622666A US 709937 A US709937 A US 709937A US 3622666D A US3622666D A US 3622666DA US 3622666 A US3622666 A US 3622666A
- Authority
- US
- United States
- Prior art keywords
- infections
- phrenosin
- resistance
- bacterial infections
- cocci
- 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.)
- Expired - Lifetime
Links
- 208000035143 Bacterial infection Diseases 0.000 title claims abstract description 11
- 208000022362 bacterial infectious disease Diseases 0.000 title claims abstract description 10
- ZXWQZGROTQMXME-DRXHHKTBSA-N 1-(beta-D-galactosyl)-N-[(2R)-2-hydroxylignoceroyl]sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O ZXWQZGROTQMXME-DRXHHKTBSA-N 0.000 title claims description 17
- 238000000034 method Methods 0.000 title claims description 16
- 241001478240 Coccus Species 0.000 claims description 4
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000007900 aqueous suspension Substances 0.000 claims description 2
- 241000191940 Staphylococcus Species 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 8
- 230000036039 immunity Effects 0.000 abstract description 8
- 239000004599 antimicrobial Substances 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 4
- 230000001939 inductive effect Effects 0.000 abstract description 2
- 241001465754 Metazoa Species 0.000 description 8
- 230000000069 prophylactic effect Effects 0.000 description 7
- 150000003408 sphingolipids Chemical class 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 241000295644 Staphylococcaceae Species 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- 206010041925 Staphylococcal infections Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 108010087702 Penicillinase Proteins 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940056360 penicillin g Drugs 0.000 description 2
- 229950009506 penicillinase Drugs 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 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
- 238000012404 In vitro experiment Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000941 anti-staphylcoccal effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
Definitions
- RESULTS F OR TREATING BACTERIAL INFECTIONS WITH PHRENOSIN Primary Examiner-Jerome D. Goldberg Attorney-Kinney and Schenk ABSTRACT A variety of substances are reported which alter host resistance to cocci bacterial infections. Nevertheless drugs which induce a high degree of resistance to these infections when administered prophylactically are not in wide use. Drugs which confer immunity to these infections for more than a week after administration are virtually unknown. Antimicrobials have been found which are effective in inducing resistance to infections due to cocci when administered prophylactically.
- This invention pertains to antimicrobials.
- the invention relates to antimicrobials effective in protecting against cocci bacterial infections.
- Bacteria such as cocci are a unique group of organisms embodying within themselves an array of yet unanswered puzzles in biology, both fundamental and experimental. They are ubiquitous in distribution and have attained extreme degrees of diversification in biological and biochemical characteristics. It is recognized that the significance of staphylococcal infections is not so much in severity, except in a few instances, as in the subtleties of the infection due to the unpredictable vagaries of these organisms.
- Penicillin G (benzyl penicillin) is still the drug of choice for the treatment of infections caused by susceptible coccic strains.
- numerous strains are known which elaborate enzymes such as penicillinase in response to the drugs and thus remain insensitive. This led to the development of semisynthetic penicillins which are not inactivated by penicillinase.
- staphylococci to the newer penicillins has been reported. Hence there is a seemingly never ending demand for anticoccic and antibacillic factors.
- compositions of this invention thus constitute a 5 significant new class of antimicrobials. It is contemplated that they will be taken orally periodically like vitamins, or by intramuscular injection, or, say, 250 mg. per day dose, based on the chemical per se, oral administration desirably being one 400 mg. tablet or pill per day.
- An advantage of the invention is that prior to periods where contact with staphylococci infec' tions are more likely, such as prior to entering a hospital, injections or tablets will be used by the physician.
- the assays were conducted using a penicillin-resistant strain, Staphylococcus aureus Original, first isolated from a case of acute tonsilitis and maintained in our laboratories for years. This strain is preserved in the lyophilized form and stored at 0 C. and stock cultures were raised on SA 1 l0 slants once in every 6 months. For testing, the inoculum was prepared from 24 hour cultures on SA 1 l0 slants at 37 C. The cells were washed and suspended in physiological saline (TC Tyrode Solution, Difco). In contrast to conventional procedures, an LD 80-90 instead of LD 50 was used in these investigations. This has been the practice in our laboratories in studies with staphylococci since lower dosages often fail to give adequate degrees of mortality. The LD 80-90 was determined by injecting groups of mice subcutaneously with different dilutions of the bacterial suspension and noting the mortality over a 5-day period.
- mice Using six groups of C3H/HeJ female mice ranging in age from 10 to II weeks, a biological assay of sphingomyelin was conducted. The animals were inoculated subcutaneously for 3 consecutive days with various amounts of sphingomyelin. On the fourth day they were challenged with a suspension of the Original Strain organism giving a 60 percent transmission. The results recorded in table I were noted.
- compositions of this invention thus constitute a signifistaphylococcal infections, but show that phrenosin is even cant new class of antimicrobials. It is contemplated that they more effective than sphingomyelin. will be taken orally periodically like vitamins, say, weekly or It was decided to assay these compounds in different mouse 30 monthly, in 250 to 500 mg. tablets. Prior to periods where strains to ascertain whether discrepancies in results would apcontact with staphylococci or streptococci infections are more pear on the basis of host differences.
- Survivors were from the groups which had been treated In the case of tablets, if desired, suitable colorants, adhewith sphingomyelin and phrenosin. Brain extract was also in- 55 sives, and lubricants will be incorporated along with a solid cluded in this work in order to obtain a comparative picture.
- h ti l dil t for instance, starches, lactose,
- a method of treating bacterial Infections in mammals comprising administering to a mammal suffering from said bacterial infection an antibacterial efi'ective amount of I TABLE" 5 7O phrenosin. [smivms rechumted 59 days the first challenge] 2.
- the method of claim 1 wherein the bacterial infection is Percent mortality in due to a coccus. days 3.
- the method of claim 2 wherein the coccus is Staphylococ- Group animals 1 2 3 4 5 cus sureus.
- n the phrenosin 1s m admix- Survivors from brain extrae tfn. 7 14.2 14.2 14. 2 14.2 14.2 ture with a solid pharmaceutical diluent.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70993768A | 1968-03-04 | 1968-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3622666A true US3622666A (en) | 1971-11-23 |
Family
ID=24851919
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US709937A Expired - Lifetime US3622666A (en) | 1968-03-04 | 1968-03-04 | Methods for treating bacterial infections with phrenosin |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3622666A (enrdf_load_stackoverflow) |
| JP (1) | JPS494933B1 (enrdf_load_stackoverflow) |
| CA (1) | CA952017A (enrdf_load_stackoverflow) |
| DE (1) | DE1910716A1 (enrdf_load_stackoverflow) |
| FR (1) | FR2003204A1 (enrdf_load_stackoverflow) |
| GB (1) | GB1259197A (enrdf_load_stackoverflow) |
| NL (1) | NL6903239A (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1986003971A1 (en) * | 1985-01-14 | 1986-07-17 | Syn-Tek Ab | Antiviral agents |
| US20060134182A1 (en) * | 2003-01-20 | 2006-06-22 | Nieuwenhuizen Willem F | Sphingolipids for improvement of the composition of the intestinal flora |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0477270A1 (en) * | 1989-06-15 | 1992-04-01 | Med-Tal, Inc. | Prevention and treatment of microbial infection by phosphoglycerides |
| TW261533B (enrdf_load_stackoverflow) * | 1992-07-16 | 1995-11-01 | Kirin Brewery | |
| KR100301890B1 (ko) * | 1997-02-05 | 2002-01-09 | 사토 야스히로 | 스핀고당지질을함유하는동결건조조성물및그의제조방법 |
| KR101442047B1 (ko) * | 2005-09-22 | 2014-09-18 | 유키지루시 메그밀크 가부시키가이샤 | 스핑고미엘린 함유 의약, 음식품 또는 사료 |
-
1968
- 1968-03-04 US US709937A patent/US3622666A/en not_active Expired - Lifetime
-
1969
- 1969-03-03 DE DE19691910716 patent/DE1910716A1/de active Pending
- 1969-03-03 JP JP44015459A patent/JPS494933B1/ja active Pending
- 1969-03-03 NL NL6903239A patent/NL6903239A/xx unknown
- 1969-03-04 FR FR6905874A patent/FR2003204A1/fr not_active Withdrawn
- 1969-03-04 CA CA044,623A patent/CA952017A/en not_active Expired
- 1969-03-04 GB GB1259197D patent/GB1259197A/en not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| Chemical Abstracts 52: 13916 e (1958). * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1986003971A1 (en) * | 1985-01-14 | 1986-07-17 | Syn-Tek Ab | Antiviral agents |
| AU580136B2 (en) * | 1985-01-14 | 1989-01-05 | Symbicom Aktiebolag | A second-step virus binding receptor |
| US4859769A (en) * | 1985-01-14 | 1989-08-22 | Symbicom Ab | Antiviral agents |
| US4980462A (en) * | 1985-01-14 | 1990-12-25 | Symbicom Aktiebolag | Antiviral agents |
| US20060134182A1 (en) * | 2003-01-20 | 2006-06-22 | Nieuwenhuizen Willem F | Sphingolipids for improvement of the composition of the intestinal flora |
| US8703172B2 (en) * | 2003-01-20 | 2014-04-22 | Nederlandse Organizatie voor Toegepastnatuurwetenschappelijk Onderzoek TNO | Sphingolipids for improvement of the composition of the intestinal flora |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS494933B1 (enrdf_load_stackoverflow) | 1974-02-04 |
| GB1259197A (enrdf_load_stackoverflow) | 1972-01-05 |
| FR2003204A1 (enrdf_load_stackoverflow) | 1969-11-07 |
| DE1910716A1 (de) | 1969-10-02 |
| NL6903239A (enrdf_load_stackoverflow) | 1969-09-08 |
| CA952017A (en) | 1974-07-30 |
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