http://patft.uspto.gov/netacgi/nph-P...1&Sect2=HITOFF &p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL& RefSrch=yes&Query=PN/7671091
http://patft.uspto.gov/netacgi/nph-P...1&Sect2=HITOFF &p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL& RefSrch=yes&Query=PN/7671091
DETAILED DESCRIPTION OF THE INVENTION
In one embodiment of the invention, a pharmaceutical vasodilator composition is administered to a male patient to cause a prolonged engorgement of the penis in order to cause expansion of the erectile tissue. The pharmaceutical composition comprises a pharmaceutically acceptable vasodilator for causing a prolonged suitable engorgement of the penis, together with a pharmaceutically acceptable diluent or carrier. The vasodilator may be a drug typically used to treat erectile dysfunction, but administered at a similar or higher dosage or sequentially as two or more lesser doses to achieve a prolonged period of engorgement followed by an additional period of lesser engorgement. Optionally, the agent may be administered at a slow rate with a micro infusion pump, time-release device or other self-injection technique or device. During a treatment, the penis should be engorged for a minimum of 3 hours and typically there is one treatment per day, and at least four treatments per week.
A very hard firm erection which is usually preferred for erectile dysfunction will have more veno-occlusive obstruction of the circulation and the reduced flow of fresh oxygenated blood into the erectile tissue will limit the maximum duration that the erection can be safely maintained. A softer less firm response can be safely and comfortably maintained for a greater length of time than a full erection.
The vasodilator drug may be one which either directly or indirectly causes vasodilation and may be classified, without limitation, in one of the following categories, namely, nitrovasodilators, ACE inhibitors, angiotensin receptor antagonists, phosphodiesterase inhibitors, direct vasodilators, adrenergic receptor antagonists, calcium channel blocking drugs, alpha blockers, beta blockers, lymphthomimetics, vitamins, organic nitrates, serotonin receptor-blocking agents, angina blocking agents, other hypertensive agents, cardiac stimulating agents, agents which improve renal, vascular function, sympathomimetic amine and mixtures thereof. For example, the drug may be any suitable vasodilator, such as papaverine, chlorpromazine, atropine, phentolamine, and prostaglandin E1, and salts, derivative, precursors, pharmaceutically active sequences or regions, peptidomimetics, mimetics, and mixtures thereof. Other drugs which may cause vasodilation include, without limitation, any of the following: niacin, nitroglycerine, nilatrin hydrochloride, pentoxyphylene, phenoxybenzamine, dichlophenac, hydralazine, hydrazaline, hydrochlorothiazide, sodium nitroprusside, isoxaprine hydrochloride, epoprostenol sodium, nylidrin hydrochloride, tolazoline hydrochloride, nicotinyl alcohol, phentolamine mesylate, phentolamine hydrochloride, yohimbine, thymoxamine imipramine, verapamil, isoxsuprine, naftidrofuryl, tolazoline, hydroisosorbide, dibenamine dinitrate, captopril, enalapril, enalaprilat, quinapril, lisinopril, ramipril, losartan, amrinone, milrinone, vesnarinone, nicorandil, prazosin, labetalol, celiprolol, carvedilol, bucindolol, nifedipine, dobutamine, minoxidil, nylidrin, and salts, derivatives, precursors, and mixtures thereof. Preferably, the vasodilator is prostaglandin E1, alone or with other vasodilators, administered as one or more doses that are typically lower than what would be used to treat erectile dysfunction. For example, the prostaglandin E1 may be administered by intracavernosal injection in a dosage range of 0.2 mcg to 500 mcg, more preferably in a dosage range of 0.5 mcg to 100 mcg. For example again, the prostaglandin E1 may be administered by an implantable sustained release drug or device in a dosage range of 0.5 mcg to 20,000 mcg, more preferably in a dosage range of 2 to 10,000 mcg (mcg=microgram).
Optionally, the patient may be treated with an additional, second pharmacological agent, to potentiate the effect of the composition which causes a prolonged, engorgement of the penis. Here, the second agent is called a "potentiator". The potentiator may be administered as part of the composition, separately from the composition, or a combination of both.
The potentiator may be a pharmacological agent or combination of agents that promote cellular processes that result in biological and/or mechanical creep and ultimately induce remodelling of the connective tissues that help define the size and shape of the penis. In addition, an agent which increases solubility of collagen may be used as a potentiator. Agents with very specific mechanisms of action may be used, or other agents with pleomorphic mechanisms of action, such as relaxin or growth hormone which trigger diverse mechanisms to induce growth in the penis may be used. For example, agents may be administered that facilitate the elongation of collagen fibres and accelerate the turnover remodelling rates of collagen through numerous mechanisms. For example, D-penicillamine and dimethyl sulfoxide (DMSO), which promote the elongation of collagen by inhibiting or interfering with inter- and intramolecular collagen cross-linkage may be used. Other agents include, but are not limited to, relaxin, insulin like growth factors, growth hormone, metalloproteinases or metalloproteinases agonists or promoters of collagenase activity, tissue inhibitors of matrix metalloprotenases (TIMPs) other agents that increase collagen solubility, prostaglandins, corticosteroids, or aminobenzoate potassium, a commercial brand being known as Potaba.TM.. Preferred prostaglandins are prostaglandin F2 alpha and prostaglandin E2. Also included are pharmaceutically active sequences, peptidomimetics, or mimetics above the above-listed molecules.
Relaxin directly and indirectly triggers a cascade of complex biochemical and cellular effects that can cause general morphological changes to genitalia. Prostaglandins such as prostaglandin F2 alpha and prostaglandin E2 have similar effects. This invention includes the mediators of these cascades as potentiators.
Collagen is a component of the extracellular matrix (ECM), which is a dynamic entity with many other components (e.g., proteoglycans, fibronectin, elastin, laminin, etc.) that functions as a storage reservoir for cytokines and enzymes and interacts intimately with surrounding cells to provide a structural scaffold and an efficient biochemical communication network within tissues. Enzymes primarily responsible for ECM remodeling are the Matrix MetalloProteinases (MMPs), which break down ECM components, and the Tissue Inhibitors of Matrix MetalloProteinases (TIMPs). Maintenance of a balance of ECM synthesis and MMP/TIMP activity in tissues is required for normal homeostasis; imbalances will generally lead to diseases or developmental problems such as scleroderma, periodontal disease, restenosis, osteoarthritis, liver cirrhosis, glomerulonephritis, and ulceration.
Relaxin is a 6 kDa peptide hormone that is structurally similar to insulin; the prohormone form consists of B-C-A chains (20 kDa), and the C chain is proteolytically excised in `mature` relaxin. However, unlike many other pro-hormones, pro-relaxin retains its biological activity. The profile of conserved amino acid sequences among various species such as pig, human, whale, porpoise, and shark suggests that relaxin is an ancient hormone with a unique molecular evolutionary history. The most recognized effect of relaxin on target cells is induction of MMP expression and inhibition of collagen synthesis.
Historically, relaxin has been classified as a "pregnancy hormone" that acts on reproductive tissues only during pregnancy, preparing the female for parturition by "relaxing" the pelvic ligaments and tendons. However, recent evidence suggests that relaxin may be classified as a "master hormone" that also induces biochemical, changes in a number of non-reproductive tissues. In addition to up-regulating MMP expression in reproductive tissues such as the cervix and placenta relaxin up-regulates expression of MMP-1 and MMP-3 in lung fibroblasts, skin fibroblasts, and fibrocartilaginous cells. Relaxin receptors are found in the brain heart, skin, nipples, small intestine, mammary gland, blood vessels, and testes. The bioactivity of relaxin is unique when compared with other cytokines that affect ECM remodeling.
The potentiator or potentiators may be administered as part of the composition, separately from the primary composition, or a combination of both. For example, the potentiator Potaba.TM. may be administered orally and the composition administered intracavernosally. Optionally, the potentiater may be administered locally into the cavernosal tissue, externally but adjacent the cavernosal tissue by injection into the surrounding connective tissue or the dorsal suspensory ligament of the penis, or a combination. The potentiator may be an agent which activates the androgen receptor, which is involved with male sexual development and function. For example, the potentiator may be an androgen hormone such as, but not limited to, the naturally occurring androgens and derivatives thereof, including androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androstenediol, androstenediol-3-acetate, androstenediol-17-acetate, androstenediol-3,17-diacetate, androstenediol-17-benzoate, androstenediol-3-acetate-17-benzoate, androstenedione, dehydroepiandrosterone (DHEA; also termed "prasterone"), sodium dehydroepiandrosterone sulfate, 4-dihydrotestosterone (DHT; also termed "stanolone"), 17.beta.-hydroxyandrost-4-en-3-one, 5.alpha.-dihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, oxandrolone, stanozolol and testosterone; pharmaceutically acceptable esters of testosterone and 4-dihydrotestosterone, typically esters formed from the hydroxyl group present at the C-17 position, including, but not limited to, the enanthate, propionate, cypionate, phenylacetate, acetate, isobutyrate, buciclate, heptanoate, decanoate, undecanoate, caprate and isocaprate esters; and pharmaceutically acceptable derivatives of testosterone such as methyl testosterone, testolactone, oxymetholone and fluoxymesterone. Testosterone and testosterone esters, such as testosterone enanthate, testosterone propionate and testosterone cypionate, may be used. The aforementioned testosterone esters are commercially available or may be readily prepared using techniques known to those skilled in the art or described in the pertinent literature.
The aforementioned androgenic agents are selected from the group consisting of naturally occurring androgens, synthetic androgens, and derivatives thereof, and any agent that will stimulate the androgen receptor directly or indirectly. The active agents may be incorporated into the present dosage units and thus administered in the form of a pharmaceutically acceptable derivative, analog, ester, salt, or amide, or the agents may be modified by appending one or more appropriate functionalities to enhance selected biological properties such as penetration through mucosal tissue. Preparation of esters, as noted in the preceding section, involves functionalization of hydroxyl and/or carboxyl groups that may be present, as will be appreciated by those skilled in the arts of pharmaceutical chemistry and drug delivery. For example, to prepare testosterone esters, the 17-hydroxyl group of the testosterone molecule is generally caused to react with a suitable organic acid under esterifying conditions, such conditions typically involving the use of a strong acid such as sulfuric acid, hydrochloric acid, or the like, and a temperature sufficient to allow the reaction to proceed at reflux. Esters can be reconverted to the free acids, if desired, by using conventional hydrogenolysis or hydrolysis procedures.
Testosterone is the principal steroid secreted by the testes and is the primary circulating androgen found in the plasma of males. Testosterone is converted to 4-dihydrotestosterone(DHT) by the enzyme 5 alpha-reductase in many peripheral tissues. DHT is thus thought to serve as the intracellular mediator for most androgen actions (Zhou, et al., Molec. Endocrinol. 9:208-18 (1995)). Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-Methyl-Nortestosterone ("MENT'") and its acetate ester.
Optionally, a mechanical device such as a ring may be used at the base of the penis to prolong retention of the composition within the penis. The mechanical device may also be used to prolong retention of any pharmacological agent used to potentiate the effect of the composition, i.e., the potentiator.
The pharmaceutical composition is administered to the patient in a pharmaceutically acceptable dosage and schedule of administration to achieve engorgement which lasts for several hours. The treatment regimen typically begins with the physician determining a first dosage amount to try on a patient to determine that subject's erectile responsiveness to the composition. The amount of the first dosage given will be determined, among other things, by the route of intended administration, the age of the man, the recent history of erectile function of the man, and pre-existing health conditions of the man.
To achieve an erectile response, one or more doses may be administered which are typically of similar or a higher amount than that used to treat erectile dysfunction. This should produce a full erection. Alternatively, two or more lesser doses may be administered to achieve a prolonged engorgement of about 40-75% response. Optionally, a combination of similar, higher, and lesser doses may be administered.
It is the duration of a full erection and the subsequent period of engorgement that determines the starting dose. The penis may be visually inspected and palpated to determine the extent of the response to the composition.
A desirable first erectile response for the purposes of this invention is considered to be at least a 45-100% response for a period of at least two hours, but preferably 3-6 hours duration. For intracavernosal injections, first dosage amounts may range from about 0.5 mcg to about 30 mcg of prostaglandin E1, and more preferably from 1 mcg to 6 mcg. If a 70-100% erection is not achieved within 20 minutes of the first test dosage amount administered by intracavernosal injection, a second injection of less, the same or more of the composition as the initial test injection, depending on if there was any response with the first test dosage. For example, if there was a 55-70% response, a "booster" shot of a lesser amount than the first dosage amount may be administered. If there was no response, the same or more than the amount of the first dosage amount may be administered. Other administrative routes may take a longer or shorter time to achieve the initial response. The dosage is gradually increased by an amount that is usually within 50% to 200% the previously administered dosage until a satisfactory response is achieved. Using these general guidelines a maximum of two injections are administered per visit.
If an erection is not achieved with the first or second injection, one or more additional appointment/visits on another day may be required to establish the dose.
Once the correct response is achieved, it will be followed by one or more confirmatory doses on subsequent visits. Once a starting dosage amount of a single or a sequence of two or more injections is established that provides a response of suitable duration, the dosage may be titrated, for example, to provide the subject with an initial 70%-100% engorgement followed by a further period of reduced engorgement of at least 40% for at least 3-6 hours. The firmness of the penis generally decreases over this period, but will be at least 40% engorged for at least 3 and preferably up to 6 hours and less than 75% engorged for the majority of the time.
Depending on the subject's response to the treatment, higher dosages may be used as determined by the physician. However, it should be noted that higher dosages may increase the risk of a very firm erection that may cause ischemia. If the veno-occlusive mechanism closes to an extent that it reduces the inflow of fresh oxygenated blood for a sufficient period to cause pain and tissue damage it can cause a medical condition called a priapism. The risk of priapism can be reduced by using smaller multiple doses. The subject's condition should be monitored and the dosage adjusted to ensure that the patient experiences a prolonged period of engorgement, rather than a prolonged full erection, which may lead to priapism and associated health complications.
Subjects should have careful instruction in the signs and symptoms of priapism, and have access to 24 hour emergency medical treatment to allow prompt treatment and eliminate any risks of ischemia to the penis.
A physician should closely monitor the subject's response to medication, to determine signs of edema, tenderness, and other early signs that the dose is excessive and needs adjusting.
If lumps or unexpected thickening of the penis occurs during treatment, the patient may have to stop or suspend treatment for a period of time. Once the appropriate dosage for a given patient has been determined, the treatment may be self-administered under the close supervision of a properly trained physician or health professional.
The treatment is repeated over a period of time sufficient to cause a permanent increase in the length and girth of the patient's penis. The treatment may comprise administration with the composition alone, or in conjunction with potentiator. For example, the treatment may be repeated daily or at least two times a week over a period of several weeks or at least one month. More preferably, the treatment may be repeated at least 3-4 times a week for a period of at least 3 months. For treatment periods of between 12 and 18 months, an increase of at least 5% may be achieved in the length and girth of an erect penis, and increases of at least 30% or even at least 50% in the length and girth of an erect penis may be achieved. Active treatment for more extended periods, e.g. 24 months, may yield greater results.
The subject may continue with normal sexual activities during the course of treatment. In fact, due to the prolonged elevation in penile blood flow, patients using this treatment will experience a very significant increase in erectile function. During treatment, patients will have dramatic improvements in the frequency, strength and duration of their own naturally stimulated erections. Men using this treatment will require much lower levels of sexual arousal and stimulation to produce and maintain their own naturally induced erections.
The pharmaceutical composition and/or potentiator may be administered using a variety of different methods known to those of skill in the art, including administration by direct manual injection to the cavernosal tissue by needle, auto-injector, slow sustained injection pumps, high pressure injection devices, urethral suppository, implantable sustained release drug or device, microinfusion pump or systemically by oral administration, parenteral administration such as subcutaneously or intra muscularly, intravenous administration by needle, auto-injector, slow sustained injection pump, high pressure injection device or implantable sustained release drug device, or topical administration, such as through the use of creams, lotions or patches with suitable additives for transdermal delivery. Most conveniently, the treatment with the vasodilators is administered by intracavernosal injection. Optionally, the pharmaceutical composition and/or potentiator may be administered by a deep injection that is well below the dermis and subcutaneous tissues which is administered into the dense connective tissue that surround the erectile tissue of the penis. This may be in the form of a depot oil. The pharmaceutical composition and/or potentiator may also be administered to the dorsal suspensory ligand of the penis.
For example, relaxin may be administered by intracavernosal injection at a dosage ranging from 0.01 to 50 mcg/kg body weight/day, more preferably at a dosage ranging from 0.02 to 10 mcg/kg body weight/day, or topically at a dosage ranging from 5 to 1000 mcg/kg body weight/day, more preferably at a dosage ranging of 25 to 400 mcg/kg body weight/day, or by injection into the dense connective tissue surrounding the erectile tissue of the penis at a dose ranging from 0.01 to 50 mcg/kg body weight/day, more preferably at a dosage ranging from 0.02 to 10 mcg/kg body weight/day, and more preferably still, at a dosage ranging from 0.02 to 1 mcg/kg body weight/day.
Kits of the composition are part of this invention. The kit may include a pharmaceutical composition of the invention and written instructions as to how and when to administer the composition in order to achieve an enlarged penis by repeated treatments, over a period of weeks or months. Optionally, the kit may include a pharmaceutical composition of the invention with written and possibly videotaped/cd rom (compact disc) video instructional information and/or be accompanied by oral instructions from a health professional as to how and when to administer the composition in order to achieve an enlarged penis. Preferably, the patient does not self-administer the composition without the supervision of a health professional. Optionally, the kit may also include an agent which will potentiate the effects of the pharmaceutical compositions of this invention. In this case, written, video format instructions or oral instructions will be included as to how to use the agent to potentiate the effect of the composition.
Without binding itself to any particular theory, applicant believes that this invention works by inducing biological creep (induction of cellular processes for tissue remodelling and cellular growth) and, to a lesser degree, biomechanical creep (mechanical microscopic tearing and viscoelastic stretching of the connective tissue). The pharmaceutical composition of the present invention induces prolonged penile engorgement, which results in a significant increase in the arterial blood flow through the penis. This increase in blood flow can safely activate the veno-occlusive mechanism that then expands and pressurizes the erectile tissue for several hours, while providing a constant flow of fresh oxygenated blood flow into the penis. This avoids the complications and health risks caused by priapism and ischemia and safely applies prolonged, continuous stimulation of the cellular processes necessary to induce maximal rates of biological and mechanical creep to enlarge the penis with minimal distortions in the shape or architecture of the penis. The potentiators may be co-comittently administered to accelerate the rate of the cellular processes that remodel the tissues of the penis in the growth/enlargement process.
In order that the invention may be better understood, preferred embodiments will now be described in the following examples.
A male patient, age 41, was treated with intracavernosal injections of a vasodilator, prostaglandin E1, on a regular basis (approximately four to five times per week) over an 18 month treatment period. A sufficient quantity was administered to maintain a prolonged engorgement of an erectile response between 40-75% over a period of several hours, generally 3 to 6 hours. The quantity of medication was adjusted from time to time in accordance with the patient's response, which was monitored at least weekly.
The size of the patient's fully erect penis increased from 5.8 inches to 8.6 inches in length (about an 48% increase) and 3.7 inches to 5.8 inches in girth (about an 56% increase) over the 18-month treatment period. Following the discontinuation of this treatment, the erect penis length remained stable for two years at over 81/2 inches. Treatment was re-institued combining intracavernosal injections 3-4 times per week of a mixture of testosterone (0.5 mg) and vasodilators with low dose oral Potaba (500-1000 mg) 3-4 times per day. After a short treatment period of 21/2 months, the patient's erect penis was over 9 inches in length, which means he has gained an additional 0.4-0.5 inches in length (about an 6% increase). The total increase in length was therefore about 3.2 inches (about an 55% increase) in length.
A male patient, age 30, was treated with intracavernosal injections of the vasodilator on a regular basis (approximately four to five times per week) over a 6-month treatment period. A sufficient quantity was administered to maintain a prolonged engorgement over a period of about 3 to 6 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiator potaba (aminobenzoate) (1000 mg/4 times per day) was administered orally to the patient for the last 60 days of treatment.
The patient's erect penis increased from 5.6 inches to 7.7 inches (about an 38% increase) in length and 3.2 inches to 5.3 inches (about an 65% increase) in girth over the 6-month treatment period.
A male patient, age 52, was treated with separate intracavernosal injections of vasodilators, Papavarine, phentolamine and prostaglandin E1, on a regular basis, selected from treatments of 0 to 4 times per week, over a 7 month treatment period along with daily subcutaneous injections of a prostaglandin F analogue. A sufficient quantity of vasodilator was administered to maintain a prolonged engorgement of an erectile response greater than 70% for 3.5-5 hours duration. The quantity of medication was adjusted from time to time in accordance with the patient's response, which was monitored initially weekly then monthly once the patient had mastered the IC technique and the responses were consistently of the same duration.
The size of the patient's fully erect penis increased from 5.0 inches to 6.3 inches in length, i.e. about a 26% increase, over the 7-month treatment period. Following the discontinuation of this treatment, the erect penis length remained stable.
A male patient, age 34, was treated with intracavernosal injections of a triple mix of the vasodilators Atropine, Chlorpromazine and Papavarine on a regular basis (approximately two to five times per week) over a 4-month treatment period. A sufficient-quantity was administered to maintain a prolonged engorgement of 60-90% over a period of about 3 to 4.5 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiator, Potaba.TM.--potassium aminobenzoate (1000 mg/3-4 times per day) was administered orally starting 1 month before starting the IC injections of the vasodilators Atropine, Chlorpromazine and Papavarine.
After 5 months of treatment the patient's erect penis increased from 6.0 inches to 7.1 inches (about an 18% increase) in length.
A male patient, age 44, was treated with intracavernosal injections of a quadruple mix of the vasodilators prostaglandin E1, Atropine, Chlorpromazine and Papavarine on a regular basis (approximately two to four times per week) over a 4-month treatment period. A sufficient quantity was administered to maintain a prolonged engorgement over a period of about 3 to 5 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiator dihydrotestosterone 5% ointment was administered orally starting two weeks before starting the IC injections of the vasodilators Atropine, Chlorpromazine and Papavarine and prostaglandin.
After 4 months of treatment the patient's erect penis increased from 5.2 inches to 6.5 inches (about a 25% increase) in length.
A male patient, age 44, was treated with intracavernosal injections of the vasodilator phentolamine on a regular basis (approximately two to four times per week) over a 4-month treatment period. Phentolamine was frequently combined with indirect vasodilating effects of oral Viagra to produce and maintain a prolonged engorgement of 60-90% over a period of about 3 to 5 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiator dihydrotestosterone gel was administered orally starting two weeks before starting the IC injections of the vasodilators Atropine, Chlorpromazine and Papavarine and prostaglandin.
After 4 months of treatment the patient's erect penis increased from 5.2 inches to 6.5 inches (about a 25% increase) in length.
A male patient, age 72, was treated with intracavernosal injections of the quadruple mix of the vasodilators prostaglandin E1, Atropine, Chlorpromazine and Papavarine on a regular basis (approximately two to four times per week) over a 3-month treatment. The indirect vasodilating effects of oral Cialis and Levitra were sometimes added to the quadruple mix of the vasodilators prostaglandin E1, Atropine, Chlorpromazine and Papavarine to produce and maintain a prolonged engorgement of 60-85% over a period of about 2.5 to 3 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiators Potaba 1000 mg 4.times./day orally and prostaglandin F topically were also used with the vasodilators. After 3 months of treatment the patient's erect penis increased from 6.5 inches to 7.1 inches (about a 9% increase) in length.
A male patient, age 47, was treated with intracavernosal injections of a triple mix of the vasodilators Atropine, Chlorpromazine and Papavarine on a regular basis (approximately three to four times per week) over a 6-month treatment period. A sufficient quantity was administered to maintain a prolonged engorgement of an erectile response between 60-95% over a period of several hours, generally 3 to 4.5 hours. The quantity of medication was adjusted from time to time in accordance with the patient's response, which was monitored initially weekly. After 2 months of treatment subcutaneous injections of testosterone 14-20 mg into the penis were added as an accelerator.
The size of the patient's fully erect penis increased from 5.2 inches to 6.0 inches in length (about a 15% increase) over the 6 month treatment period.
A male patient, age 52, was treated with intracavernosal injections of the quadruple mix of the vasodilators prostaglandin E1, Atropine, Phentolamine and Papavarine on a regular basis (using IC medications approximately two to four days per week) over a 3-month treatment. Since the maximum duration of the engorgement of the erection from a single dose was only 45 to 80 minutes, the patient used two to three separate IC injects spaced through out the treatment days to achieve a total i.e. cumulative daily duration of 3 to 4 hours. The indirect vasodilating effects of oral Cialis and Levitra were sometimes added to the quadruple mix of the vasodilators prostaglandin E1, Atropine, Chlorpromazine and phentolamine to produce and maintain a prolonged engorgement of 60-85% over a period of about 3 to 4 hours. The quantity of medication was adjusted in accordance with the patient's response. The potentiator Potaba 1000 mg 4.times./day orally was used with the vasodilator. After 4 months of treatment the patient's erect penis increased from 5.4 inches to 6.1 inches (about a 13% increase) in length and 4.4 to 5.1 inches in circumference (about a 16% increase in circumference).
A male patient, age 27, was treated with intracavernosal injections of a prostaglandin E1 on a regular basis (approximately two to five times per week) over a 3-month treatment period. Due to a sensitivity to Prostraglandin E1 causing aching and pain at higher doses, the maximum tolerated dose which produced a comfortable erection was only lasting 90 to 120 minutes. The patient used two separate IC injects spaced throughout the treatment days to achieve a total daily cumulative engorgement duration of 3 to 4 hours. The quantity of medication was adjusted in accordance with the patient's response. The 15 mg of the potentiator Dihydrotestosterone was injected subcutaenously into the penis daily throughout the treatment period. After 3 months of treatment the patient's erect penis increased from 6.3 inches to 7.1 inches (about an 13% increase) in length.
Although various examples of combined elements of the invention have been described, it will also be understood that these are not intended to be exhaustive and features of one embodiment may be combined with those of another, and such other combinations are contemplated to be within the scope of the invention disclosed herein.
All publications and other documents mentioned herein are hereby incorporated by reference into this specification.
While preferred embodiments of the invention have been illustrated and described, it will be appreciated that various changes and modifications can be made therein without departing from the spirit and scope of the invention as defined by the following claims.
This application claims priority from U.S. application No. 60/398,562, filed Jul. 26, 2002, and PCT/CA2003/001139, filed Jul. 25, 2003.
FIELD OF INVENTION
This invention is in the field of penis enlargement.
BACKGROUND OF INVENTION
There are various circumstances under which a male subject may desire the permanent enlargement of the length and/or girth of his penis, in both its flaccid and erect states. Penis enlargement may be desired for medical reasons, for example, if a patient is unable to penetrate during coitus due to an unusually small penis size; for cosmetic reasons; or to improve a person's self-esteem.
There have been many attempts to create a safe and effective means for achieving permanent penis enlargement, including the use of external weights and suction devices. The use of external weights is cumbersome and impractical and produces localized compressive forces that may cause localized ischemia. Furthermore, use of weights often leads to a thinning of the penis and may even impair penis function.
Suction devices are also cumbersome and impractical to wear on a prolonged basis, have limited effectiveness, and pose a number of risks. Suction devices produce localized compressive forces that may cause localized ischemia. Vacuum seals with pressure over 20 mm Hg can obstruct capillary flow and inhibit tissue perfusion. Suction devices often come with warnings that the devices should not be used for periods exceeding 20-30 minutes, which may be insufficient to achieve the desired result. Use of suction devices can also result in the thickening of the skin and accumulation of fluid in the superficial layers of the skin and subdermis. The skin of the penis is hypermobile, and only very loosely connected to deeper connective tissues and structures that comprise the erectile tissues of the penis. The skin of the penis can readily separate from the fibrous connective tissue capsule which encloses the erectile tissue of the penis when externally applied suction forces are applied to the penis.
Also, any suction forces applied to the penis will have a proportionately larger effect on the skin, and the forces on the deeper structures diminish dramatically. The increase in the surface area of the skin causes the suction forces to be applied mainly to the skin, not to the erectile tissue and the surrounding capsule of the cavernosal tissue. As a result, the skin can be thickened as fluid is extravasated and there is typically no, or only a limited enlargement, of the underlying erectile tissues of the penis. Use of suction devices may also cause the separation of the skin from the subdermis and the formation of seromas or blisters on the penis. The application of suction devices to the penis causes the extravasation of red blood cells out of the vascular spaces and into the extracellular compartments. If vacuum devices are applied for extended periods of time, this may lead to a significant pigmentation of the penis. Applying a suction device repeatedly may cause the deposition of large amounts of iron and other hemoglobin degradation products in the tissue of the penis causing hemosiderosis, which ultimately results in fibrosis. Furthermore, erectile dysfunction may result from prolonged use of these devices.
it is also linked in google to this forum, add http & www ;
One of the post on the forum:
I understand: I just posted it, so you guys could read it...Here is more info from another person...
I promised to write to the board after I returned from my trip to visit Dr. Adams, the owner of the 5159 patent. Originally, I had intended to simply write a letter about what he offered, and his thoughts on PE. However, after just responding to Chanceya1975, it seems that the experience levels of the members of this board is an unknown. Some, or perhaps most, are apparently not well versed in the medical side of male health issues, so I am going to write a much more basic letter than originally intended so that those who are just starting out will have more of their questions answered. To those that are well versed, I apologize for making this letter longer than necessary and for being redundant. My goal is simply to prevent the errors that have already happened to some board members from happening to others.
Before reading this letter, it would be helpful if you were to read the letter that I just sent to Chanceya1975, as this will serve as one reason for the depth and style of this letter.
As this letter may be used as "road map" for beginners, I will try to go into details that are basic to men's health, but with which I did not discuss with Dr. Adams.
Dr. Kenneth W. Adams, MD, DDS, owns and does business under the trade name MTMC (Male Therapeutic Medical Clinic) Male Therapeutics. His address is 1200 Sheppard Avenue, East, Suite 509, North York, Ontario, M2K 2S5 His phone number is 416-693-3905. His web site is Drs4men.com
I was given a pamphlet about Dr. Adams from one of the PA's (physician assistants) there that describes Dr. Adams experience. Dr. Adams is around 50 years old. In his past history he was worked "as the medical director for one of the largest and busiest men's clinics in North America" Further, "Dr. Adams has assessed, treated, optimized the sex hormones and sexual performance in over 30,000 men" Dr. Adams is also a surgeon, but restricts his surgery to hair transplantation. Since he went into private practice, he does not do many surgeries anymore.
Dr. Adams has a fair sized clinic that is set up to be as discrete for the patient as possible. He employs three clerical people, two physician assistants and a business manager (accountant). His office is in a nice, relatively new office building just off the 41 freeway in the greater Toronto, Canada area.
In addition to the more traditional men's clinic items of specialty, which are fixing low libido, ED, hair loss, Dr. Adams also offers a penis enlargement program.
The clinic is set up for his needs. The office is clean and neat, and the staff is friendly. To give the patients the maximum amount of discretion, the office has quite a number of small rooms that I would describe as "cubicles." Each is about 5' wide about 9 feet deep. There is a comfortable chair, stool, and TV that is hooked up to cable TV. This is designed so that you will not come into contact with any other patient in the office. You are escorted to your cubicle, given the clicker to choose what you want to watch on TV and wait to see the next person who will treat you. While you are in your cubicle, others may be in the hallway, but you are not in a hallway when any other patient is. When you are in your cubicle, or in an office, the doors are always closed. Occasionally, you can hear some other patient talking, but that is quite infrequent.
When you first meet one of the PA's you are taken to another cubicle and the tv is turned to a channel that has a CD playing a recording of Dr. Adams talking about different subjects. One DVD deals with ED. Another deals with Hormones, and if you are there for PE, one deals with the basics of PE. This seems a nice way to educate beginners, and answer the basic questions that most guys have that come to a clinic like that for the first time.
When the DVD's finish, you are then taken to one of the PA's office for a health history. I met "Riz" (short for Riswah- and as you can guess, Riswah is of Indian heritage) who is a very nice guy. He is outgoing, easy to talk to, and knowledgeable. The PA will take down your medical history, take blood samples if needed, take your blood pressure and generally do what is needed so that when you meet Dr. Adams, your time is productive.
At this point, I am a bit different than the average patient, and so my experience was a bit different. I have ED, which was caused by a fall that damaged my pudential artery, so I already have prescriptions for Caverject, and more. I am also in an anti aging program that supplies me with Growth Hormone, as well as Testosterone. I brought all of my medicines, discussed them with Riz and shortened my time there considerably. The normal patient would have those areas explored as well, and it would serve the patient well to know what his various hormone levels are. My blood tests from my anti aging program are extensive, so all that they needed was there.
For the normal patient, blood levels may be taken if needed, although for strictly for a PE program that would not be needed. It may well be advantageous though for a patient to do the blood tests so that a "baseline" set of values can be obtained. This will be helpful later in life, as in the aging process our hormone levels decline.
The PA's also have teaching aids (dildo's) to teach proper injection technique, how to use an auto injector, penis measurement, etc. They will also teach how to withdraw the contents from a bottle of quad mix without ruining the bottles seal.
After the PA is finished with you, you meet Dr. Adams. He is a very nice guy. He is rather quiet, and has a quick smile. He will assess the information given, discuss your goals with you, give you an examination, and for the PE process, give you an injection of tri mix to begin the titration process. The process is timed, with you being taken back to a cubicle to watch more TV and keep up with the length of time that you are erect.
Should you have a priapism, Dr. Adams has another injection that will end the erection in less than 10 minutes, and has them ready to go at all time. The goal for the first step of titration is simply to obtain an initial reaction. The next day, you will be given another injection, only this time, you will give it to yourself with Dr. Adams, or one of the PA's watching to see that you do it correctly. The length of your erection is also timed, while you wait in a cubicle.
The goal time for your erection is TWO HOURS. This will probably surprise most readers after they have read the patent and all the talk of long term erections. This length of time is only for the PE patients, as the typical ED patient will be titrated for a one hour erection.(although certainly when you gain experience, extending that erection time is simply a trial and error method). The important part here is that everyone has a different "titration curve" or to put it another way, the amount of quad mix that you need just depends upon your own body's needs.
Ok, at this point, I am going to digress a minute and make a pitch for you, the reader to consider becoming Dr. Adams patient, or alternatively to make a check list so that you can assess what you may receive from another physician in this area.
With Dr. Adams you get:
1. Complete discretion in your medical wants. You will not see another patient while there, so for you guys who are shy, you will not be embarrassed.
2. You will get complete medical care in regards to your overall health as it relates to PE, can get blood work done as a check, or if you feel like your libido (desire for sex) is less than it could be, they can check that and get you fixed up at the same time.
3. Will give you the right product to give you an erection so that you will not end up as our member Chanceya1975 did by going to his physician.
4. Teach you correct injection technique, and guys, this is IMPORTANT.
5. Titrate your dosage of quad mix so that you know how much you need for future activity.
6. Since they are the only clinic that I know of with a PE program, you can be completely honest in your intentions with the Doctor.
7 They supply the quad mix and needles as part of the program. So you know what you are getting. You can also buy an auto injector from them to make injections easier.
All in all, it is a pretty good case for being Dr. Adams patient. Now of course, traveling to Toronto, Canada may not be feasible. If it is not, then at least you know what to look for when you assess a men's health clinic.
And should you decide to visit a typical men's health clinic, do tell them that you have performance anxiety rather than ED. The reason is that (hopefully) they will realize that you do not have a problem in GETTING an erection, so the dosage to KEEP the erection is much lower. One of our members did to to a men's clinic, but the doctor did not put a lot of thought into the dosage amount, and started him with a dosage for a person with ED. As a result, he got a priapism, and that is not good.
There is one more thought about this that is worth considering. We men tend to be a bit stoic at times. When something happens to our health, we tend to want to just hope that things get better and wait as long as possible before seeking professional medical help. When it is our penis that is the problem, a whole lot of us are modest, or perhaps afraid to risk our ego to have anyone know what we are really doing. These are bad traits when it comes to medical problems that involve our penis, as you most certainly can be hurt by injection incorrectly. Well, with Dr. Adams, there is no need to have modesty, or ego enter into the equation. You and the Dr. both know exactly what you are doing, and the only question is your health in achieving your goals. I submit that this is the best care standard that is out there, and one that for the average guy, works the best.
Ok, back to my experience with Dr. Adams. In my discussions with the Dr. we discussed the basic idea behind the PE method. The term that is used is "tissue remodeling." The tunica is made up mainly of collagen. Collagen is like fibers. They start out laying next to each other but quickly become "cross linked" which makes them stronger, but still pliable. By unlinking the collagen (partially) and stretching the penis, it is like opening the weave in cloth. Only in this case, the collagen goes back together with some space in it that is soon filled with more collagen.
For the basic program, the most active chemical is PGE-1 which not only gives an erection, but also "unlinks" a portion of collagen, allowing for the stretching that follows to slowly expand the tissue length of the penis. So the basic program is simply the two hour erection that is induced with quad mix, and 30 minutes a day of stretching.
At first, I had a hard time accepting that, because I have used caverject for12 years and have not gained any length, and in fact, have lost length. Well, the reason was that I was not stretching during that time, as to the reason that I did not gain, and the reason that I lost length was due to poor blood flow (caused by the accident I had which damaged my pudential artery). Certainly as I pondered that I guess that I have accepted it, and it certainly makes PE easy. Results that are anticipated are 3/8" per month on average. So the basic program is to use the quad mix four times a week to obtain a two hour erection, with stretching exercises every day for 30 minutes a day. In the stretching exercises Dr. Adams suggests that the whole hand be used to grasp the penis, that the penis be "milked" at first to get some blood into the head of the penis, and that 70% of all stretching be pulling down, with the rest being equally divided between left, right, up and out directions.
I did not mention the fact that I had a copy of his patent with me as I did not want to bring up anything that may have any degree of controversy with it. But in our conversation about "accelerating" the results we did discuss:
1. Growth hormone. In my case, I already take GH as part of my anti aging program. Normally, I inject into the fat on the side of my waist. I asked him about using GH in the program. He said that in Canada, GH is very difficult to get and must be used only for cases of dwarfism. So basically, GH is not available in Canada for prescription. This would also apply to growth factors such as IGF-1 or 2, so I did not bring those up. Since I was already on GH he suggested that I inject above the central tendon (at the 12 o'clock position) so that the injection is sub cutaneous, but not in the tendon. He also warned me about my not wanting to inject deeply as I would hit the artery, and that would take a lot of effort to stop the bleeding there. So a "tenting" of the skin was suggested. I have done one shot that way, and it requires a bit of manual dexterity, but all in all, it is easy enough..
2. We discussed the use of the hormone Relaxin as a tissue remodeler. For humans, Relaxin is GREAT tissue remodeler, and is used in the birthing process. It is what opens the vagina so that a baby can come down the vagina during birth. So, its role in opening collagen is well documented. The sad thing about Relaxin is that human recombinant Relaxin has not been manufactured since 2002. It was manufactured as a potential aid for Scleroderma patients, but it did not help much, so the manufacturing of it stopped. And this means that it is not available. I mentioned to Dr. Adams that I have porcine relaxin and he was surprised to hear that. I am sending him a bottle for him to take a look at and to see if it is beneficial to a PE effort.
3. Testosterone and DHT. In my case, I also take Testosterone in a creme form for my anti aging program. Dr. Adams suggested that I apply some of my creme to my penis and testicles as that will convert it to DHT and that it would be helpful. As to adding it to his PE program he does not do that very much. DHT is also supervised in Canada, as it is in the US. He did say that it would be helpful to use in if I had it.
4. I did not ask about DMSO since it is so cheap, and easy to get, Anyone wanting to try it out should have little problems in getting it, and since it is included as being helpful in the patent, it did not seem worth the effort to discuss.
I had a lot of other thoughts as I was there, but they were mostly my curiosity about how the patent was put together, who magnumforce was, etc. but as they are not relevant to a PE effort, I did not go there.
I hope that I have been helpful to the members of the board.
Pin your dick who doesn't want a bigger third leg but
Effect of insulin-like growth factor-I treatment on serum androgens [/B] and testicular and penile size in males with Laron syndrome (primary growth hormone resistance)
Auteur(s) / Author(s)
LARON Z. (1) ; KLINGER B. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Endocrine and Diabetes Research Unit, Schneider Children's Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, ISRAEL
[B]Résumé / Abstract
Serum gonadotrophins, androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 ***956;g/kg per day to the boys and 120 ***956;g/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 ***956;g/kg per day. Stopping the IGF-I administration in this patient. according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.Revue / Journal Title
European journal of endocrinology (Eur. j. endocrinol.) ISSN 0804-4643
Source / Source
1998, vol. 138, no2, pp. 176-180 (22 ref.)
Langue / Language
This is in men with Laron syndrome. So it may not be as applicable but still it shows IGF-1 affecting sex organs.
Clicking this I expected it to be a troll. Interesting idea. I wouldn't do it. Even if I needed it. But then again idk insecure people will do crazy ****.
In reality injecting your penis can be safe. Google caverject.
For similar reasons that most people want more muscle, people want more penis.
I kinda feel like people are afraid to talk about it as if they will be suspected of having a small penis.