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WO1991000094A1 - Nouveau systeme d'injection de papaverine - Google Patents

Nouveau systeme d'injection de papaverine Download PDF

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Publication number
WO1991000094A1
WO1991000094A1 PCT/DK1989/000163 DK8900163W WO9100094A1 WO 1991000094 A1 WO1991000094 A1 WO 1991000094A1 DK 8900163 W DK8900163 W DK 8900163W WO 9100094 A1 WO9100094 A1 WO 9100094A1
Authority
WO
WIPO (PCT)
Prior art keywords
papaverine
sulphate
impotence
compartment
disc
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.)
Ceased
Application number
PCT/DK1989/000163
Other languages
English (en)
Inventor
Finn Tranberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to PCT/DK1989/000163 priority Critical patent/WO1991000094A1/fr
Publication of WO1991000094A1 publication Critical patent/WO1991000094A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/28—Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle
    • A61M5/284—Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle comprising means for injection of two or more media, e.g. by mixing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/16—Male reproductive, genital organs
    • A61M2210/167—Penis

Definitions

  • Papaverine has been used therapeutically for the last 5 years in the treatment of impotence.lt is given as an intracavernosal injection-usually in the form of papaverine sulphate in doses of 20 mg to 120 mg.
  • Papaverine sulphate is the compound of choice because of its low toxicology and very good solubility in water.
  • Papaverine hydrochloride is also in use,but the salt has a less solubility in water compared with the sulphate. The chemistry and the therapeutical effects are otherwise the same.Because of that we will concentrate on the papaverine sulphate only.
  • Papaverine sulphate(papaverini sulfas) (C Intel n H Union,NO. )-H-SO. ,5H»0 is an odourless white crystalline powder with a slightly bitter, burning taste. It is hygroscopic.Mp 90 C.pK 6, 4.Soluble 1 in 1 of water,1 in 20 of ethanol,1 in 5000 of ether and 1 in 2 of chloroform.Mol 866, 9.A 2% solution in water has a pH of 3.
  • Papaverine is on the contrary a tasteless white crystalline powder and practically insoluble in water.These facts have a great significance as shown later.Mol 339,4.A solution in water is naturally neutral.Mp 148 C.
  • the hydrogen ion being bound to nitrogen in papaverine.lt follows then that at pH 6,4 the concentration of papaverine will be 50%,at pH 5,4 10% and at pH 4,4 1% etc.
  • the commercial papaverine sulphate solution used therapeutically has a very low concentration of papaverine and a high concentration of papaverine,H .pH range from 2,5 to 3,5.
  • This new papaverine injection system eliminates or reduces significant these sideeffects and complications,but first there will be a presentation and explication of the sideeffects and complications.
  • Pain is developed when the highly acid and the high in concentration of papaverine,H papaverine sulphate/hydrochloride solution is injected into the corpus cavernosum.
  • the new system is non-acid and very low in concentration of papaverine,H and it is therefore painless. e.
  • the main advantage of the new papaverine injection system is therefore its good tolerance in connection with the human body.
  • the new papaverine injection system in the treatment of impotence is in principal a single unit consisting of two closed compartments. he one compartment contains papaverine sulphate or papaverine hydrochloride (it can also contain a mixture of the papaverine salt and phenoxybenzamine hydrochloride/phentolamine mesylate) and the other compartment contains a base. Just before use are the two compartments mixed and the two solutions therein and immediately thereafter is the mixture injected into the human corpus cavernosum penis.
  • papaverine If papaverine sulphate and a base are mixed papaverine will crystallize out because of its low solubility in water.
  • the mixture is quite clear for more than 5 in. and pH is more than 5, 3.
  • the mixture is injected into the human corpus cavernosum and the clinical result is compared with a similar injection only containing water instead of sodium hydrogencarbonate. he results are quite identical - as to the quality and duration of eretion.
  • papaverine sulphate (calculated as papaverine 30 mg/ml) is mixed with 0,53 ml sodium hydrogencarbonate (with a concentration of 14 mg/ml) - same mol. he papaverine fell out as a microcrystalline dispersion.
  • the mix ⁇ ture injected into the human corpus cavernosum and the clinical result is compared with a similar injection only containing wa ⁇ ter instead of sodium hydrogencarbonate.
  • the injection containing sodium hydrogencarbonate gives no pain injected into the human corpus cavernosum.Otherwise are the results quite identical - as to the quality and duration of erection.
  • the second part of this new invention is concerned with the practical design and the production of the system.
  • Figure 1 shows in principle the design of the new papaverine injection system in the treatment of impotence.This system is especially suitable when a semistable mixture of the solutions x and y is wanted but no actual fell out wanted.This is because of the smooth surfaces in the interior of the system.It is on the other hand also superior when a fell out is wanted compared to a system where the separation between compartment x and y is in the form of a plastic coating.
  • A is a rubber tube closed in one end.Its interior coated with an extensible plastic.
  • B is a plastic disc with a smooth surface and rounded ends.
  • C is a unit of C-l,C-2,C-3 and C-4.
  • C-l is a plastic disc with no rounded ends in order to prevent it from slipping from the tube(A).It can be secured by an external ring if desired. In its meddle is the needle(C-2 )attached firmly.
  • C-2 is a fine needle of a proper lenght.
  • C-3 is a wire fitting exactly to the interior of the needle.
  • C-4 is a plastic cap.
  • the plastic cap fits exactly to the ex ⁇ terior of the needle (C-2). he plastic cap and the wire(C-3) are attached together firmly.
  • In the junction between the plastic cap and the plastic disc(C-l) is a layer of lake to insure sterility.
  • the new papaverine injection system works as follows : The user or patient pushes the plastic disc (B) to a perpendicular position. The plastic disc is held in place only by the tension of the rubber wall. The diameter of the plastic disc disc (B) being greater than that of the interior diameter of the rubber tube(A).
  • Figure 2 illustrates the ease of producing the system.A handy and an airtight system suitable for many purposes but made to improve the treatment of impotence.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

De la papavérine que l'on injecte dans les corps caverneux du pénis est utilisée pour le traitement de l'impuissance. Elle est aujourd'hui injectée sous forme de sulfate de papavérine ou d'hydrochlorure de papavérine. Ceci comporte des complications très graves à cause de l'acidité et de la concentration élevées de la papavérine, H+. Elle provoque la fibrose des corps caverneux du pénis, de la douleur, ainsi que la formation de cicatrices et de sclérose. Il a été démontré qu'une solution semi-stable ou séparée peut être obtenue par l'addition d'une base, cette solution ayant le même effet thérapeutique par rapport à la qualité et à la durée de l'érection tout en évitant les complications précitées, ce qui représente une amélioration importante du traitement de l'impuissance. Afin d'injecter le mélange précité, on a élaboré un dispositif en une seule unité à deux compartiments d'injection et de mélange. Les deux solutions dans les compartiments x et y sont séparées par un disque (B). Le disque (B) est maintenu en place par la raideur de la paroi de (A) mais peut facilement être amené à une position perpendiculaire qui permet aux solutions de se mélanger. L'avantage principal du système est représenté par les surfaces intérieures lisses qui servent à créer une substance séparée microcristalline régulée, et par le fait qu'il s'agit d'un système fermé, évitant le risque de contamination.
PCT/DK1989/000163 1989-06-28 1989-06-28 Nouveau systeme d'injection de papaverine Ceased WO1991000094A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/DK1989/000163 WO1991000094A1 (fr) 1989-06-28 1989-06-28 Nouveau systeme d'injection de papaverine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/DK1989/000163 WO1991000094A1 (fr) 1989-06-28 1989-06-28 Nouveau systeme d'injection de papaverine

Publications (1)

Publication Number Publication Date
WO1991000094A1 true WO1991000094A1 (fr) 1991-01-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1989/000163 Ceased WO1991000094A1 (fr) 1989-06-28 1989-06-28 Nouveau systeme d'injection de papaverine

Country Status (1)

Country Link
WO (1) WO1991000094A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027841A1 (fr) * 1996-01-31 1997-08-07 Gist-Brocades B.V. Utilisation de compositions comprenant des composes stabilises et efficaces sur le plan biologique
WO1998034842A1 (fr) * 1997-02-07 1998-08-13 Biodome Recipient distributeur multichambre pour le stockage d'au moins deux substances, le melange extemporane de celles-ci et la distribution du melange
WO2010040560A3 (fr) * 2008-10-10 2010-06-10 Milux Holding Sa Stimulation d'érection du pénis
US8852153B2 (en) 2008-10-10 2014-10-07 Peter Forsell Stimulation of penis erection
US8874215B2 (en) 2008-10-10 2014-10-28 Peter Forsell System, an apparatus, and a method for treating a sexual dysfunctional female patient
US8961448B2 (en) 2008-01-28 2015-02-24 Peter Forsell Implantable drainage device
US9060771B2 (en) 2008-01-29 2015-06-23 Peter Forsell Method and instrument for treating obesity
US9072907B2 (en) 2008-10-10 2015-07-07 Peter Forsell Heart help device, system, and method
US9192474B2 (en) 2008-10-10 2015-11-24 Peter Forsell Stimulation of penis erection
US9504785B2 (en) 2005-11-02 2016-11-29 Peter Forsell Implantable infusion devices and methods
US9949812B2 (en) 2009-07-17 2018-04-24 Peter Forsell Vaginal operation method for the treatment of anal incontinence in women
US10219898B2 (en) 2008-10-10 2019-03-05 Peter Forsell Artificial valve
US10583234B2 (en) 2008-10-10 2020-03-10 Peter Forsell Heart help device, system and method
US10952836B2 (en) 2009-07-17 2021-03-23 Peter Forsell Vaginal operation method for the treatment of urinary incontinence in women
US11123171B2 (en) 2008-10-10 2021-09-21 Peter Forsell Fastening means for implantable medical control assembly
US11344297B2 (en) 2019-02-28 2022-05-31 Covidien Lp Surgical stapling device with independently movable jaws
FR3158505A3 (fr) 2024-01-19 2025-07-25 L'oreal Contenant de distribution à double chambre

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2610628A (en) * 1950-05-09 1952-09-16 Compule Corp Plural-compartment admixing vial for segregated storage of ingredients of solutions and liquid mixtures
US3494359A (en) * 1969-03-17 1970-02-10 Silver Jules Two compartment syringe with a single barrel
US4437858A (en) * 1978-01-16 1984-03-20 Ty Perla J Separator disc and hypodermic syringe incorporating the same and method
DE3637157A1 (de) * 1985-11-01 1987-05-21 Byk Gulden Lomberg Chem Fab Arzneimittel zur behandlung erektiler dysfunktionen
EP0266968A2 (fr) * 1986-11-03 1988-05-11 Gérard G. Cohen Onguent gélifié contenant un agent vasodilatateur

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2610628A (en) * 1950-05-09 1952-09-16 Compule Corp Plural-compartment admixing vial for segregated storage of ingredients of solutions and liquid mixtures
US3494359A (en) * 1969-03-17 1970-02-10 Silver Jules Two compartment syringe with a single barrel
US4437858A (en) * 1978-01-16 1984-03-20 Ty Perla J Separator disc and hypodermic syringe incorporating the same and method
DE3637157A1 (de) * 1985-11-01 1987-05-21 Byk Gulden Lomberg Chem Fab Arzneimittel zur behandlung erektiler dysfunktionen
EP0266968A2 (fr) * 1986-11-03 1988-05-11 Gérard G. Cohen Onguent gélifié contenant un agent vasodilatateur

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A.G. FISHBURN: "An Introduction to Pharmaceutical Formulation", 1965, PERGAMOS PRESS (OXFORD), see pages 126-127. *
UROLOGIC CLINICS IN NORTH AMERICA, Vol. 15, No. 1, February 1988, (Philadelphia), ABRAHAM AMI SIDI: "Vasoactive Intracavernous Pharmacotherapy", see pages 95-101. *
UROLOGIC CLINICS OF NORTH AMERICA, Vol. 14, No. 2, MAy 1987, (Philadelphia), T.R. MALLOY, B. MALKOWICZ: "Pharmacologic Treatment of Impotence", see pages 297-305. *

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027841A1 (fr) * 1996-01-31 1997-08-07 Gist-Brocades B.V. Utilisation de compositions comprenant des composes stabilises et efficaces sur le plan biologique
US6117433A (en) * 1996-01-31 2000-09-12 Dsm N.V. Use of compositions comprising stabilized biologically effective compounds
WO1998034842A1 (fr) * 1997-02-07 1998-08-13 Biodome Recipient distributeur multichambre pour le stockage d'au moins deux substances, le melange extemporane de celles-ci et la distribution du melange
FR2759348A1 (fr) * 1997-02-07 1998-08-14 Biodome Recipient distributeur multichambre pour le stockage d'au moins deux substances, le melange extemporane de celle-ci et la distribution du melange
AU724953B2 (en) * 1997-02-07 2000-10-05 Biodome Multi-chamber dispensing container for storing at least two substances, the extemporaneous mixture of these substances, and distribution of the mixture
US6189688B1 (en) 1997-02-07 2001-02-20 Biodome Multi-chamber dispensing container for storing at least two substances, the extemporaneous mixture of these substances, and distribution of the mixture
CN1080685C (zh) * 1997-02-07 2002-03-13 比奥多公司 存储至少两种物质的多腔室分配容器
RU2184058C2 (ru) * 1997-02-07 2002-06-27 Биодом Многокамерный сосуд-дозатор для хранения, по меньшей мере, двух веществ, смешивания этих веществ непосредственно перед употреблением и дозирования смеси
US9504785B2 (en) 2005-11-02 2016-11-29 Peter Forsell Implantable infusion devices and methods
US8961448B2 (en) 2008-01-28 2015-02-24 Peter Forsell Implantable drainage device
US9060771B2 (en) 2008-01-29 2015-06-23 Peter Forsell Method and instrument for treating obesity
US9526649B2 (en) 2008-10-10 2016-12-27 Peter Forsell Method and instrument for treating obesity
US10583234B2 (en) 2008-10-10 2020-03-10 Peter Forsell Heart help device, system and method
US8874215B2 (en) 2008-10-10 2014-10-28 Peter Forsell System, an apparatus, and a method for treating a sexual dysfunctional female patient
US9072907B2 (en) 2008-10-10 2015-07-07 Peter Forsell Heart help device, system, and method
US9192474B2 (en) 2008-10-10 2015-11-24 Peter Forsell Stimulation of penis erection
US9370656B2 (en) 2008-10-10 2016-06-21 Peter Forsell System, an apparatus, and a method for treating a sexual dysfunctional female patient
US8852153B2 (en) 2008-10-10 2014-10-07 Peter Forsell Stimulation of penis erection
US11123171B2 (en) 2008-10-10 2021-09-21 Peter Forsell Fastening means for implantable medical control assembly
WO2010040560A3 (fr) * 2008-10-10 2010-06-10 Milux Holding Sa Stimulation d'érection du pénis
US10219898B2 (en) 2008-10-10 2019-03-05 Peter Forsell Artificial valve
US8870823B2 (en) 2008-10-10 2014-10-28 Peter Forsell Stimulation of penis erection
US10952836B2 (en) 2009-07-17 2021-03-23 Peter Forsell Vaginal operation method for the treatment of urinary incontinence in women
US9949812B2 (en) 2009-07-17 2018-04-24 Peter Forsell Vaginal operation method for the treatment of anal incontinence in women
US11344297B2 (en) 2019-02-28 2022-05-31 Covidien Lp Surgical stapling device with independently movable jaws
FR3158505A3 (fr) 2024-01-19 2025-07-25 L'oreal Contenant de distribution à double chambre

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