US2868692A - Anthelmintic polymethylenepiperazine and method of using same - Google Patents
Anthelmintic polymethylenepiperazine and method of using same Download PDFInfo
- Publication number
- US2868692A US2868692A US585160A US58516056A US2868692A US 2868692 A US2868692 A US 2868692A US 585160 A US585160 A US 585160A US 58516056 A US58516056 A US 58516056A US 2868692 A US2868692 A US 2868692A
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- US
- United States
- Prior art keywords
- polymethylenepiperazine
- ascarids
- pinworms
- piperazine
- dose
- 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
- 238000000034 method Methods 0.000 title description 4
- 230000000507 anthelmentic effect Effects 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- 244000000013 helminth Species 0.000 claims description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 13
- 241000498255 Enterobius vermicularis Species 0.000 description 11
- 206010014881 enterobiasis Diseases 0.000 description 11
- 230000036765 blood level Effects 0.000 description 6
- 229960005141 piperazine Drugs 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 229960003506 piperazine hexahydrate Drugs 0.000 description 3
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 3
- 241000244185 Ascaris lumbricoides Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000244030 Toxocara canis Species 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- LTGINMMNLIIFJW-UHFFFAOYSA-N 2-methylidenepiperazine Chemical compound C=C1CNCCN1 LTGINMMNLIIFJW-UHFFFAOYSA-N 0.000 description 1
- 241000760149 Aspiculuris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- -1 Polymethylene piperazine Polymers 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000001418 larval effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
Definitions
- This invention relates to new compositions. offmatter. More particularly, it relates to therapeutic compositions of polymethylenepiperazine-and a carrier. for the elimination of helminths such as pinworms andascarids.
- An object. of; the present-invention is; to 'prepare a composition-capable: of producing; ;a 'high .blood level and being: eilective' against :helminthst such: as; pinworms: and ascarids.
- A-- furtherobject is-to prepare a composition which will maintain a high;blood level.- of druggforv a longer period of time.
- a still. further object is to prepare a composition-whichz will be. absorbed less completely and/or more slowly in-order to reach and afiect helminthls: such as:- pinwormstand? ascarids-i in. the more terminal portions of the digestivettractf. 1
- polymethyle'ne piperazine 50-100 mg./kgm.
- the peak blood level was reached five to eight hours after-administration.
- piperazine under similar conditions, reaches peak blood levels during the second hour after" administration.
- the presenceof polymethylenepiperazinei in the blood was detectable up to"'24 hours. after administrae tion;;whereas the'presenceofpiperazine'was not-so detectable; The.
- the amount of single doses or daily doses to be given will vary with the size of the man or animal to be treated, but should'b'e such' as to give a proportionate dosage of 1 to 500mg. per kgm. of body weight. ln terms of total weight of drug, this is usually from about 0.1 g. to 10.00. g. per dosageunit. In largeranimals, obviously, largerjdosage units maybe desirable.
- Polymethylenepipera'zine was given in a single, oral dose to-mice naturally infected with pinworms of the species Aspicularis tetraptera, which resembles human pinwornis.
- the mice were killed and necropsied several days after treatment and the intestinal tract examined foiapinworms. Activity is'indicated when a large proportion. ofthe. treated. miceireveal few or no worms at necropsy, as compared withuntreated controls.
- Table ll illustrates the results obtained:
- compositions containing polymethylenepiperazine are effective against dog ascarids (Toxocara canis), as shown in Table III illustrating the results obtained and also comparing them with piperazine hexahydrate and piperazine hydrochloride.
- Polymethylene piperazine is also effective against Ascaris lumbricoides in guinea pigs. A summary of tests carried out is shown in Table IV.
- the compound polymethylenepiperazine can be combined with a carrier and dispensed in any of the usual dosage unit forms of pharmaceutical preparations; for example, tablets, capsules, pills, suspensions, as a powder, or in any other desirable form in the therapeutic quantities hereinbefore given. It may be in a dosage unit form for a single, daily, therapeutic dose or in smaller units for multiple doses or in larger units for division into single doses. Obviously, in addition to the therapeutic product, there may be present excipients, binders, fillers and other therapeutically inert ingredients necessary in the pharmaceutical preparation.
- edible carriers For use in treating animals it may be combined with edible carriers, such as feed stuffs, etc.
- a therapeutic composition useful in the treatment of helminths in dosage unit form comprising from 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure per dosage unit and an edible carrier.
- a therapeutic composition for oral administration useful in the treatment and elimination of pinworms and ascarids in dosage unit form comprising from 0.1 g. to
- a therapeutic composition useful in the treatment of pinworms and ascarids in dosage unit form comprising from 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure and a solid pharmaceutical carrier, said composition being in tablet dosage unit form.
- a therapeutic composition in dosage unit form useful in the treatment of pinworms and ascarids comprising from about 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure and a significant amount of pharmaceutical carrier.
- a method of maintaining higher blood levels of piperazine useful in the treatment of pinworms and ascarids which comprises administering in dosage unit form from 1 mg. to 500 mg. per kgm. of body weight of a polymethylenepiperazine of the following unit structure N H N-on v and an edible carrier.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent AJNTHELMINTIC POLYMETHYLENEPIPERAZINE AND METHOD OF USING SAME Frederick L. Bach, Jr., and Redginal I. Hewitt, Pearl:
No Drawing. Application May 16, 1956 Serial No. 585,160
6 Claims. (Cl. 167-55) This invention relates to new compositions. offmatter. More particularly, it relates to therapeutic compositions of polymethylenepiperazine-and a carrier. for the elimination of helminths such as pinworms andascarids.
An object. of; the present-invention: is; to 'prepare a composition-capable: of producing; ;a 'high .blood level and being: eilective' against :helminthst such: as; pinworms: and ascarids. A-- furtherobject is-to prepare a composition which will maintain a high;blood level.- of druggforv a longer period of time. A still. further object is to prepare a composition-whichz will be. absorbed less completely and/or more slowly in-order to reach and afiect helminthls: such as:- pinwormstand? ascarids-i in. the more terminal portions of the digestivettractf. 1
Wet have now found that: the: above. objects: can. be attained. by theme: of:polyrnethylenepiperazine, whichi'i's effective? in:. removing hehninths; particularly.- pinworms and ascarids. While pipera'zinehexahydrate? hastbeen used in the past for pinworms; it has the undesirable property of being hygroscopic, and, therefore, it is troublesome to combine with other materials, such as a carrier. On the-other hand, polymethylenepiperazine-is -a-stable,- tastelss; granular powder; insoluble in" water, which can be" easilymixed with other materials. Poly/methylenepiperazine, being substantially tasteless, is= more palatable than piperazin'ehexahydrate. When both'fediiand fasted dogs are given a single oral dose of. polymethyle'ne piperazine (50-100 mg./kgm.)*the peak blood level was reached five to eight hours after-administration. In contrast, piperazine, under similar conditions, reaches peak blood levels during the second hour after" administration. Furthermore; the presenceof polymethylenepiperazinei in the blood was detectable up to"'24 hours. after administrae tion;;whereas the'presenceofpiperazine'was not-so detectable; The. following table summarizesthisinforma tionz' TABLEI Piperazine blood 'levels in non-fasted dogs [Base equivalent dose: 100 mgr/kgm: oral]? Tests to determine excretion showed that 100% of the piperazine administered was excreted in the urine, whereas, of the polymethylenepiperazine administered, about 2. 60% was excreted in the urine and about 30% detected by assay in the faeces. Polymethylenepiperazine offers therapeutic advantages: over other forms. of piperazine, since it gives desirable blood levels for longer periodsof 5 time against'worms in the tissues, and its slower and/0r less. complete absorption favors greater elfectiveness in treating pinworms and other worms infecting the lower intestinal tract.
The amount of single doses or daily doses to be given will vary with the size of the man or animal to be treated, but should'b'e such' as to give a proportionate dosage of 1 to 500mg. per kgm. of body weight. ln terms of total weight of drug, this is usually from about 0.1 g. to 10.00. g. per dosageunit. In largeranimals, obviously, largerjdosage units maybe desirable.
' The compound polymethylenepiperazine was described in Beilstein, volume XXIII, page 6, 1936, quoting Rosdalsky, I. Prak. chem. (2) 53,'p. 22 (1896) and Berichte, volume 30, pages3043-3045. The compounds described in these references .are a polymethylenepiperazine of the following unit structure Its use as an anthelmintic in the treatment of pinworms or ascaridshas not been described. Methods of pre.- paring the compound are described in the above reference and in the= chemical literature.
Polymethylenepipera'zine was given in a single, oral dose to-mice naturally infected with pinworms of the species Aspicularis tetraptera, which resembles human pinwornis. The mice were killed and necropsied several days after treatment and the intestinal tract examined foiapinworms. Activity is'indicated when a large proportion. ofthe. treated. miceireveal few or no worms at necropsy, as compared withuntreated controls. The followlng Table ll illustrates the results obtained:
TABLE II Percent of j Single oral mice with Compound Test N0. dose, N0. Sur- O-5 worms I mgz/kgm. vivals at necropsy- Aspiculuris Polyrnethylene- 3453B39 500 10110 100 1.0/10 100 10/10 90 10,110 100 10/10 80 10/10 lO/lO 0 10/10 60 10/10 40 10/10 30 10/10 20 9/10 22 Polymethylene- 10/10 100 piperazme.
The present compositions containing polymethylenepiperazine are effective against dog ascarids (Toxocara canis), as shown in Table III illustrating the results obtained and also comparing them with piperazine hexahydrate and piperazine hydrochloride.
TABLE III Efiects of polymethylenepiperazine against dog ascarids (Toxocara canis), as compared with piperazine hexahydrate and hydrochloride After- No.
Ascarids Percent Dog. Oral Dose, Total Retained Ascarids No. mgJkgm. 1st 2nd 3rd. at N ec- Passed Dose Dose Dose ropsy (Total) 214 Polymethylenepiperazine"..- 12.5, b 25 19 a 4 23 100 d 12. 5, 25, b 50 7 3 3 13 l 93 12. 5, 25, b 50 0 1 3 4 0 100 a 100 10 6 63 906 Piperazine hexahydrate. a 100 9 9 1 90 922 do 100 4 4 4 50 130 do 100 6 6 1 86 127 Piperazine hydrochloride. 5 100 9 9 15 40 a Single dose.
Sequential treatment, single doses, with seven days rest between increments.
a Died third day after second dosecause of death unknown. d Three-eight days after last dose. No emesis noted with any of the doses used.
Polymethylene piperazine is also effective against Ascaris lumbricoides in guinea pigs. A summary of tests carried out is shown in Table IV.
TABLE IV Effects of polymethylenepipearzine against larval Ascaris lumbricoides in guinea pigs Experimentally infected with 2000 embryonated A. lumbricqides ova per animal.
Approximately one week after inoculation.
The compound polymethylenepiperazine can be combined with a carrier and dispensed in any of the usual dosage unit forms of pharmaceutical preparations; for example, tablets, capsules, pills, suspensions, as a powder, or in any other desirable form in the therapeutic quantities hereinbefore given. It may be in a dosage unit form for a single, daily, therapeutic dose or in smaller units for multiple doses or in larger units for division into single doses. Obviously, in addition to the therapeutic product, there may be present excipients, binders, fillers and other therapeutically inert ingredients necessary in the pharmaceutical preparation.
For use in treating animals it may be combined with edible carriers, such as feed stuffs, etc.
We claim:
1. A therapeutic composition useful in the treatment of helminths in dosage unit form comprising from 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure per dosage unit and an edible carrier.
2. A therapeutic composition for oral administration useful in the treatment and elimination of pinworms and ascarids in dosage unit form comprising from 0.1 g. to
10.00 g. of a polymethylenepiperazine of the following unit structureper dosage unit and a pharmaceutical carrier.
3. A therapeutic composition useful in the treatment of pinworms and ascarids in dosage unit form comprising from 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure and a solid pharmaceutical carrier, said composition being in tablet dosage unit form.
4. A therapeutic composition in dosage unit form useful in the treatment of pinworms and ascarids comprising from about 0.1 g. to 10.00 g. of a polymethylenepiperazine of the following unit structure and a significant amount of pharmaceutical carrier.
5. A method of maintaining higher blood levels of piperazine useful in the treatment of pinworms and ascarids which comprises administering in dosage unit form from 1 mg. to 500 mg. per kgm. of body weight of a polymethylenepiperazine of the following unit structure N H N-on v and an edible carrier.
References Cited in the file of this patent White: British Med. Iour. No. 4839, October 3, 1953, pp. 755-758.
Claims (1)
1. A THERAPEUTIC COMPOSITION USEFUL IN THE TREATMENT OF HELMINTHS IN DOSAGE UNIT FORM COMPRISING FROM 0.1 G. TO 10.00 G. OF A POLYMETHYLENEPIPERAZINE OF THE FOLLOWING UNIT STRUCTURE
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US585160A US2868692A (en) | 1956-05-16 | 1956-05-16 | Anthelmintic polymethylenepiperazine and method of using same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US585160A US2868692A (en) | 1956-05-16 | 1956-05-16 | Anthelmintic polymethylenepiperazine and method of using same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2868692A true US2868692A (en) | 1959-01-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US585160A Expired - Lifetime US2868692A (en) | 1956-05-16 | 1956-05-16 | Anthelmintic polymethylenepiperazine and method of using same |
Country Status (1)
| Country | Link |
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| US (1) | US2868692A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3057776A (en) * | 1959-03-24 | 1962-10-09 | Parke Davis & Co | Schistosomiasis treatment |
| US3067242A (en) * | 1959-08-31 | 1962-12-04 | Pfizer & Co C | Di-(n, n-dimethyloctadecylamine) pamoate |
| US20030097992A1 (en) * | 2001-10-05 | 2003-05-29 | Rubicon Scientific Llc | Animal feeds including actives and methods of preparing same |
| US20030099688A1 (en) * | 2001-10-05 | 2003-05-29 | Huber Gordon R. | Animal feeds including heartworm-prevention drugs |
| US6716448B2 (en) | 2001-10-05 | 2004-04-06 | Rubicon Scientific Llc | Domesticated household pet food including maintenance amounts of ivermectin |
| US20040180078A1 (en) * | 2002-11-13 | 2004-09-16 | Huber Gordon R. | Extruded foodstuffs having maintenance level actives |
-
1956
- 1956-05-16 US US585160A patent/US2868692A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3057776A (en) * | 1959-03-24 | 1962-10-09 | Parke Davis & Co | Schistosomiasis treatment |
| US3067242A (en) * | 1959-08-31 | 1962-12-04 | Pfizer & Co C | Di-(n, n-dimethyloctadecylamine) pamoate |
| US20030097992A1 (en) * | 2001-10-05 | 2003-05-29 | Rubicon Scientific Llc | Animal feeds including actives and methods of preparing same |
| US20030099688A1 (en) * | 2001-10-05 | 2003-05-29 | Huber Gordon R. | Animal feeds including heartworm-prevention drugs |
| US6716448B2 (en) | 2001-10-05 | 2004-04-06 | Rubicon Scientific Llc | Domesticated household pet food including maintenance amounts of ivermectin |
| US6866862B2 (en) | 2001-10-05 | 2005-03-15 | Rubicon Scientific | Animal feeds including heartworm-prevention drugs |
| US7052712B2 (en) | 2001-10-05 | 2006-05-30 | Rubicon Scientific Llc | Animal feeds including actives and methods of preparing same |
| US20060121095A1 (en) * | 2001-10-05 | 2006-06-08 | Huber Gordon R | Animal feeds including actives and methods of preparing same |
| US20040180078A1 (en) * | 2002-11-13 | 2004-09-16 | Huber Gordon R. | Extruded foodstuffs having maintenance level actives |
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