WO1991000094A1 - A new papaverine injection system - Google Patents

A new papaverine injection system Download PDF

Info

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
Application number
PCT/DK1989/000163
Other languages
French (fr)
Inventor
Finn Tranberg
Original Assignee
Finn Tranberg
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 Finn Tranberg filed Critical Finn Tranberg
Priority to PCT/DK1989/000163 priority Critical patent/WO1991000094A1/en
Publication of WO1991000094A1 publication Critical patent/WO1991000094A1/en

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.

Abstract

Papaverine given as an intracavernosal injection is used in the treatment of impotence. It is today injected in form of papaverine sulphate or papaverine hydrochloride. This has very serious complications because of the high acidity and the high concentration of papaverine, H+. It gives fibrosis of the corpus cavernosum penis, pain, scarring and induration. It is shown that a semistable or fell out solution of papaverine can be created by the addition of a base, with the same therapeutical effect as to the quality and duration of erection and without the above mentioned complications thus being a significant improvement in the treatment of impotence. To inject the above mentioned mixture there is developed a single unit two compartment injecting/mixing device. The two solutions in compartment x and y are separated by a disc (B). The disc (B) is held in place by the tension of the wall (A) but can easily be brought to a perpendicular position thus allowing the solutions to mix. The main advantage of the system is the smooth interior sufaces to create controlled microcrystalline fell out and, as it is a closed system, the non risk of contamination.

Description

A NEW PAPAVERINE INJECTION SYSTEM
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„nH„,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.
A papaverine sulphate solution in water can be symbolized as follows: papaverine,H = papaverine + H .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.
The low pH and high concentration of papaverine,H of a papa¬ verine sulphate solution in water are major problems in therapy and responsible of very serious sideeffects and complications.
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.
The clinical refences can be found in:Lue TF,Tanagho EArState of the art.Physiology of erection and pharmacological management of impotence.J Urol 137 :829 ,1987.Sidi AA.Vasoactive intracaver- nous pharmacotherapy.Urol Clin North Am 15:95,1988. Complications to intracavernous papaverine injections are listed below and at the same time the advantages of the new system are pointed out. a. Priapism or sustained erection
This phenomenon is dosage dependent.lt often happens when the patient by fault or deliberately takes a higher dose than the doctor has described.The new papaverine injection system is a single unit system and eliminates this possibility. b. Superficial infection or cavernositis
The design of the new single unit papaverine injection system where the patient does not touch or mixes himself the drug greatly reduces this complication. c. Ecchymosis/hematoma
This phenomenon is due to a faulty injection technique or the use of an inproper needle. he new system consist of an ultra- fine 30-gauge needle with a proper length for injection into the human corpus cavernosum penis. d. Pain
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. Local nontender induration at the injection site angulation of the tunica albuginea scarring and fibrotic plaques (intracavernous fibrosis) These are very serious long-term sideeffects.To a slight degree it is due to repeated trauma from needle insertion but the most important factor is the drug itself.It is the highly acid and the high in concentration of papaverine,H papaverine sul¬ phate or hydrochloride solution which promotes the formation of fibrosis.The new papaverine injection system is non-acid and very low in the concentration of papaverine,H and is therefore not promoting the formation of fibrosis.
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.
In the following we will only discuss the system containing papaverine sulphate and a base (sodium hydrogencarbonate) .
If papaverine sulphate and a base are mixed papaverine will crystallize out because of its low solubility in water. papaverine,H + HC0-. = papaverine + CO- + H„0 or papaverine,H + OH = papaverine + H20
Papaverine will crystallize out but depending of the concen¬ trations not immediately. example 1
1 ml of papaverine sulphate containing papaverine _ 30 mg/ml (papaverine,H )(it has a pH below 3)is mixed with 0,25 ml sodium hydrogencarbonate containing 14 mg/ml (isotonic 330 mOsm) .
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.
Manny similar tests have been made with papaverine sulphate in various concentrations,at various temperatures and with various bases in various concentrations.Addition of an alcohol,a glycol or other stabilizing lipid/water soluble substances will higher the pH and therefore the ratio paρaverine/papaverine,H .It is possible to make a semistable solution of papaverine sulphate with a pH just below 6 and a concentration of papaverine around 25% - the resulting concentration of papaverine,H is then 75%.
We will now show that it is possible to let the papaverine fell out and still have a solution which is injectable and have the same therapeutical effect as a similar papaverine sulphate solution. The human corpus cavernosum penis is to be regarded as a closed space filled with blood. hen a papaverine sulphate solu¬ tion is injected the buffering system of the blood will fell out the papaverine from the papaverine sulphate solution.But before this happens the toxic effect of H and papaverine,H will have taken place.If we fell out the papaverine from the papaverine sulphate solution before injecting into the corpus cavernosum we will not have the toxic local effect on the endothelium.
The papaverine fell out from the papaverine sulphate will later dissolve but it is now diluted in all of the space in the corpus cavernosum.The H will never harm the endothelium as the fell out solution is neutral. example 2
1 ml of 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.Immediately thereafter is 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.
Other concentrations of the compounds have been tested and the results are identical.
The conclusion is that a fell out solution of papaverine from a papaverine sulphate solution is suitable and has great advantages compared with a papaverine sulphate solution.lt is very important to remember that an injection of papaverine sulphate gives fibrosis.This new papaverine injection system eliminates the risk of fibrosis of the human penis.
The second part of this new invention is concerned with the practical design and the production of the system.
A system suitable for mass production at a low cost and with few components is presented.The safety and the minimizing the risk of contamination in the system for the user/patient is high. 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.
The individual components are now described.
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). The two solutions in compartment x and y are mixed by pressing to and fro the rubber tube (A) .The wire (C-3) preventing the mixture to escape.Then the plastic cap(C-4) is detached along with the wire(C-3 ) .C-4 and C-3 are sealed together because of that and also to ensure the sterility of the needle (C-2).Immediately thereafter is the mixture injected into the human corpus caverno¬ sum by pressing the rubber tube (A) .The system is held along side C-l.
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.

Claims

1. Papaverine given as an intracavernosal injection is used in the treatment of impotence.lt is today injected in the form of a papaverine sulphate or papaverine hydrochloride solution. This has very serious complications because of the high acidity and the high concentration of papaverine,H .It gives fibrosis of the corpus cavernosum penis,pain,scarring and induration.This new system is characterized_with the addition of a base crea¬ ting a semistable or fell out solution of papaverine.This mixture has the same therapeutical effect as the papaverine salt but not the complications mentioned before.It is therefore a significant improvement in the treatment of impotence.
2. To inject the above mentioned mixture there is developed a single unit two compartment injecting/mixing device Fig l.This new system is characterized_with a disc (B) separating the two solutions in compartment x and y before mixing.The disc (B) is held in place by the tension of the wall of (A) ,but it can easyly be brought to a perpendicular position thus allowing the solu¬ tions to mix.The main advantage of the system is the smooth interior surfaces to create controlled microcrystalline fell out and as it is a closed system the non risk of contamination.
PCT/DK1989/000163 1989-06-28 1989-06-28 A new papaverine injection system WO1991000094A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/DK1989/000163 WO1991000094A1 (en) 1989-06-28 1989-06-28 A new papaverine injection system

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/DK1989/000163 WO1991000094A1 (en) 1989-06-28 1989-06-28 A new papaverine injection system

Publications (1)

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Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027841A1 (en) * 1996-01-31 1997-08-07 Gist-Brocades B.V. Use of compositions comprising stabilized biologically effective compounds
WO1998034842A1 (en) * 1997-02-07 1998-08-13 Biodome Multi-chamber dispensing container for storing at least two substances, the extemporaneous mixture of these substances, and distribution of the mixture
WO2010040560A3 (en) * 2008-10-10 2010-06-10 Milux Holding Sa Stimulation of penis erection
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

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EP0266968A2 (en) * 1986-11-03 1988-05-11 Gérard G. Cohen Gelled ointment of vasodilating agent

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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 (en) * 1985-11-01 1987-05-21 Byk Gulden Lomberg Chem Fab Pharmaceutical compositions for the treatment of erectile dysfunctions
EP0266968A2 (en) * 1986-11-03 1988-05-11 Gérard G. Cohen Gelled ointment of vasodilating agent

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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 (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6117433A (en) * 1996-01-31 2000-09-12 Dsm N.V. Use of compositions comprising stabilized biologically effective compounds
WO1997027841A1 (en) * 1996-01-31 1997-08-07 Gist-Brocades B.V. Use of compositions comprising stabilized biologically effective compounds
WO1998034842A1 (en) * 1997-02-07 1998-08-13 Biodome Multi-chamber dispensing container for storing at least two substances, the extemporaneous mixture of these substances, and distribution of the mixture
FR2759348A1 (en) * 1997-02-07 1998-08-14 Biodome MULTI-CHAMBER DISPENSER CONTAINER FOR THE STORAGE OF AT LEAST TWO SUBSTANCES, THE EXTEMPORANE MIXTURE OF THE SAME AND THE DISTRIBUTION OF THE MIXTURE
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 (en) * 1997-02-07 2002-03-13 比奥多公司 Multi-chamber dispensing container for storing at least two substances, extemporaneous mixture of these substances, and distribution of mixture
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
WO2010040560A3 (en) * 2008-10-10 2010-06-10 Milux Holding Sa Stimulation of penis erection
US8870823B2 (en) 2008-10-10 2014-10-28 Peter Forsell Stimulation of penis erection
US8852153B2 (en) 2008-10-10 2014-10-07 Peter Forsell Stimulation of penis erection
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
US8874215B2 (en) 2008-10-10 2014-10-28 Peter Forsell System, an apparatus, and a method for treating a sexual dysfunctional female patient
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
US10219898B2 (en) 2008-10-10 2019-03-05 Peter Forsell Artificial valve
US11123171B2 (en) 2008-10-10 2021-09-21 Peter Forsell Fastening means for implantable medical control assembly
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

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