Improvement following bromelain injections

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gringoviajero

Firstly I must caution that I in no way endorse nor encourage anyone to follow my experiments. That said, I had very good results, evidenced in "before" and "after" photos, with the following procedures.  Please bear in mind that I have not had sex since the first symptoms appeared due to divorce and subsequent lack of a partner. Before my recent improvement, I suspect I would have had difficulty in intercourse because of my tendency to buckle.

I'll be very succinct in the history. First symptom was painful nocturnal erections, noted in 2008. Visited two urologists over the next two years; neither believed I had Peyronies Disease because there was no palpable plaque. Pain went away, bend formed slowly, still no palpable plaque.  Eventually diagnosed in 2012 when the bend became obvious at about 35-40º with a severe indent and slight hourglass.  There was a tendency to buckle when any pressure was applied.  Soft plaque fibers alone running longitudinally and laterally. Tried the usual remedies, too lengthy to list all, but including: VED, pentox, stretcher, DMSO, heat, cold, vitamin E, et al.  Never any improvement.

In 2013 I found a 2009 study paper on the efficacy of a bromelain-liposome compound for burn wound debridement (Google on "efficacy of combined cream bromelain") by Hutagalung, et al. This study demonstrated the enzymatic softening of collagen fibers while leaving healthy tissue undamaged. This led to my investigating the use of bromelain for Peyronies Disease. Eventually I found a patent application for an injectable bromelain compound filed by an Israeli company, Mediwound (Google "proteolytic extract from bromelain for treatment of connective tissue disorders").

I asked my doctor to prescribe a topical compound consisting of 10% bromelain, 3% pentoxifylline and 1% tranilast in a base of Lipoderm (original formula). I applied this to the dented area, about the size of a quarter coin, twice daily.  The skin irritation was intolerable. Based on research of bromelain's enzymatic activity, I then applied a chilled wet washcloth to the penis prior to the bromelain application.  This was to wet the skin, improving transdermal transmission, and to reduce the reaction of the bromelain with the skin before reaching the tunica.  After applying the cream, I wrapped the penis in Saran Wrap for 30-60 minutes to improve absorption.  This method reduced skin irritation considerably.

I saw no improvement.  I next followed the same procedure, but after removing the wrap, I employed a VED while under a heat lamp.  The VED routine was 3 min. on, 30 sec. off for 3 iterations, a total of 10 min. start to finish. The reasoning is that because enzymatic activity is a function of temperature, giving the drugs time to get through the cold skin to the tunica, and then applying heat while stretching the tissue, may allow the collagen fibers to soften and reshape.

There were variations on these procedures, but no other additional materials. Hand modeling such as is used in the Xiaflex therapy was also tried. This approach was taken over a period of two months with no noticeable improvement.

I then diluted about .1ml of the compound, which was too viscous to inject, with 1ml of sterile saline. I also added a few grains of azithromycine antibiotic. Using a 25g syringe, I injected .05ml in 4 aliquots of this solution into the area of indention while erect. (It probably goes without saying that this is very difficult to do.) Within a few hours the edema began and 24 hours later the swelling was pronounced.  This was expected, but nevertheless disconcerting.

Several days later, after the edema was gone, I tried using the VED, heat and hand modeling, but I quickly feared rupturing the tunica if the bromelain had softened it too much, so I soon abandoned that idea.  Within two weeks there was a noticeable reduction, albeit small, in indention and bend.

At this time I also began taking 2.5mg daily of Cialis.

A month following, I was able to get a new formulation, toning down the bromelain and increasing the pentox, of 5% bromelain, 5% pentox and 1% tranilast.  My intention was strictly to use this topically.  The bromelain was reduced because the compound was too "hot" for the skin.  Additionally, I discovered that I had not taken into account the size of the bromelain molecule, which is quite large, so I had the new compound made with Lipoderm HMW (high molecular weight) formulation.

I resumed transdermal application as before but, as before, this had no result.  I then decided to inject the compound undiluted, the Lipoderm HMW formulation being much less viscous. I performed one episode of 3 injections for a total of .15-.2ml.  The edema was pronounced but not painful.  It took 4 days to subside.  As before I did not use a VED nor a heat lamp nor modeling.  Two weeks later, the improvement was obvious.  I photographed this and sent the "before" and "after" shots to my doctor, who termed the improvement "remarkable."

It has been 5 weeks since this last injection and there seems to be some slight regression, but this is minor.  The indent is slight, the bend 25º, the erection is very firm and shows no tendency to buckle. I have no doubt now that I could have normal intercourse easily. Ironically, I now have a small lump at the injection site whereas before I had none, yet this lump has accompanied obvious improvements.  I suspect it is scar tissue, but probably not on the tunica. It is quite soft and may be a fluid sack. I am on an extended trip out of the country and will get it examined when I return.

My experience proves no more than there is some relationship between the injection of this compound and immediate improvement.  There are several reasons I can think of why this may have occured, however coincidental "natural" improvement is unlikely.  On both occasions, noticeable improvement followed the injections.  There are the obvious risks, of course, as well as triggering more scarring response. As my doctor put it, a study where n = 1 proves nothing. I am simply relating what I have done and my observations.

Mediwound does not anticipate going to market with an injectable bromelain compound for years because of Xiaflex' "orphan drug" rights.

I would be happy to answer questions or send the "before" and "after" photos, but, again, I would not encourage anyone to undertake this highly risky course of action. However, I do think this approach warrants further investigation.

gringoviajero

Three months after my second injection of the experimental bromelain-lipoderm compound, I again injected.  I felt there had been some regression.  This attempt went slightly less smoothly as needle placement was made more difficult by a rapid detumescence.  Three insertions were made in the region of the indentation.  It is not clear if any of the 3 made their way into the tunica or only nearby.  The usual 4 days of edema followed.  When the swelling subsided sufficiently I did the usual modeling.  When the swelling was gone I used the VED twice a day: 3'-30"-3'-30"-3'.  After two weeks I then applied the same compound topically.  I thoroughly wet the skin, used the VED to increase blood flow, applied a heavy dose of the compound, and wrapped the penis in Saran Wrap to improve absorbency and protect the scrotum.  This was done for 4 days, until the skin became very raw, and then abandoned.  For the remainder of the time, until one month had passed, the VED routine alone was used.

The result seems to be a return to very near normal.  The pre-Peyronies Disease length and girth have been nearly restored, within 1/8".  The bend is now a slight curve, similar to a congenital curve.  There is a palpable indentation still, but it is not visible and no longer causes a "crick."  I still take 2.5mg/daily of Cialis.  There is no tendency to buckle.  Normal intercourse should not be a problem.

My doctor says a study where n = 1 proves nothing.  True, however, I do think this approach warrants further exploration.  Mediwound in Israel is working on a bromelain-based treatment but that is years from coming to market.  One will have to consult one's doctor about experimenting with this approach.  There are serious risks.

Jonbinspain

Interesting. But, not something I would attempt. Or, I suspect, many others. It all sounds highly risky - dangerous even, if it goes wrong.  

gringoviajero

After the third injection, which showed some improvement over time, but not much, I had decided to quit while I was ahead.  However, I was left with a lump under the skin about the size of a nickel.  It was not attached to the tunica.  Believing it to be fibrin, which bromelain breaks down, I decided to do a small injection of the same bromelain compound directly into the lump.  This resulted in an abscess and the growth of a larger lump the size of a quarter.  Two days ago this was surgically removed: total cost to me $1000, another $5K to insurance.

I would not encourage anyone to follow this course, but then, obviously, there was substantial improvement as a result.  I don't regret a thing.  What I would suggest is discussion with your doctor about the use of some sort of bromelain-based compound by injection.  Mediwound already has a patent application for this.  Look at the research papers and the patent application I referenced in my first post, and talk to your doctor about taking an approach based on bromelain.  I think the complications I had may have been from using a formulation with a Lipoderm base, which of course is meant to be used topically, not injected.  Sure there's a risk, but under a doctor's supervision that can be minimized.  

stopthismadness

Google- Patents: Proteolytic extract from bromelain for the treatment of connective tissue disorders
WO 2013011514 A1

"SUMMARY OF THE INVENTION

The present invention provides a proteolytic extract obtained from bromelain for the treatment of connective tissue diseases. Particularly, the present invention provides a proteolytic extract obtained from bromelain for the treatment of connective tissue diseases which are associated with excess of collagen deposition, including Dupuytren's disease and Peyronie's disease.

It is now disclosed for the first time that a proteolytic extract obtained from bromelain comprising one or more of the cysteine proteases present in bromelain, e.g., stem bromelain or ananain, is capable of degrading native, non-denatured collagen. Unexpectedly, injection of the proteolytic extract into a Dupuytren's cord resulted in rupture of the cord while maintaining the normal healthy connective tissue intact.

The present invention further discloses that the efficacy of the proteolytic extract to rupture or dissolve Dupuytren's cords is similar to or even higher than that of collagenase. However, while collagenase may cause damage to non-diseased ligaments or tendons due to its affinity to the various types of collagen, the proteolytic extract of the present invention shows specificity to the diseased cords. Thus, the proteolytic extract of the present invention provides an improved and safe medication for connective tissue diseases which involve excess collagen deposition, particularly for the treatment of Dupuytren's disease and Peyronie's disease. Due to the fact that high concentrations of the proteolytic extract can be prepared in small volumes, such small volumes can be injected into the diseased fibrous cords or plaques, thus avoiding extravasation and damage to surrounding tissues, simplifying the clinical procedure and hence increasing patient's compliance. "

Does sound really good in theory.  

stopthismadness

gringoviajero ,

I'm curious as to how you obtained these formulations with such ease. Maybe I'm a bit ignorant or inexperienced, but I'm not entirely sure how one would find a doctor/compound pharmacist in the states that would even listen to talk about making such a concoction, much less convince him to help obtain it; and especially not if he knew there was intent to inject it into a penis.  Maybe I'm jaded by my experiences in the past with doctors. Did you show the doctor the research and patent information, and did he make you sign liability forms?

Also, it's a bit disconcerting that if Mediwound's version of the bromelain formulation were to actually work and prove safer than injectable collagenase that it's going to be blocked from the market by Xiaflex's orphan drug rights.

I'm also interested to see the before and after photos if you don't mind posting them up.  Thanks for sharing your experiment and results, it's interesting given all I've read on bromelain and collagen.

gringoviajero

I've a message in to James on how to send him my before/after shots. He will post them for me. I don't have the time anymore to devote to this, so let me be succinct.

After arriving at the formulation discussed in my first post, I forwarded the documents (studies, patent apps) to my urologist along with my suggestion we try this as a topical treatment.  We discussed it and he agreed.  There was no discussion of injections as there was no intention.  And why should there be?  Who's nutty enough to inject a compound meant for dermal use?  (Except a desperate Peyronies Disease sufferer.)

It was no problem finding a compounding pharmacy for the first formulation.  However it was near impossible to find one to fill the second formulation, the one with Lipoderm HMW.  This comes in 500g tubs and is expensive.  Nobody wanted to order a whole tub just for my 30g.  I got lucky after a LOT of searching and found a pharmacy with an open tub.  (It has since gone out of business.)

As per your comment on orphan drugs, I agree.  I can see the manufacturer's point, but I should think some arrangement could be made so that people suffering from this or any illness who could benefit from a discovery be given the chance to do so.  Why should you continue suffering from a disease for which a "cure" has been found just so that a drug company can continue to exercise their monopoly?  I should think some form of cooperation or allowance could be made, but this is really a government issue as it's not in the patent holder's interest to give way.

As a further follow-up to my complications: I had the surgery 3 weeks ago to remove "necrotizing granulomas".  The scar's 3.75" long and a drag, but it should heal OK after a few months. So far my erecton is bent the way it was before the bromelain injections, but without the indent I had back then. I optimistically suspect this may be a result of the body protecting itself during healing, as the surgeon has assured me the lesion was "superficial to Buck's fascia".  If I have internal scarring, I think it will be attached to the skin, not the tunica.  My hope is that as the incision heals, the erection will straighten.

I've learned a good bit about the penis.  There's a lot going on in there, and some of it is not well understood.  As an example, my erections created with a VED are different than those nocturnal ones created because of a full bladder, which in turn are different than those created by sexual stimulation.  It's a complex process, the erection.  I suspect I'm not alone in these differences.

I hope Mediwound, or SOMEBODY, pursues this line of research.  My complication was the result of injecting a solution not meant for injection; the Lipoderm was most likely the culprit, not the bromelain.  If I had a private pharmacist, I would have him compound a similar formula with 10% bromelain, 5% pentox and 1 or 2% tranilast in some medium appropriate for injection.  While all this sounds terribly radical, it was not done foolhardily but with much forethought and research.

I must go, but one humorous note before. When I went to the surgical urologist with the lesion and abscess, I was interviewed by his nurse practioner.  I explained at length and in detail my work with bromelain injections the preceding months.  Later, when I was leaving, they prescribed an injectable antibiotic to take daily until the surgery. The NP said I could come to the office weekdays for the injections, but weekends were difficult to find someone to give them to me.  I asked, "Well, why not just give me the antibiotic and syringes and I'll do it myself?"  She answered, "Are you comfortable with giving yourself injections?"  I'm completely serious.  So I said, "If I can give myself an injection in the erection, I think I can handle giving myself one in the ass."

gringoviajero

Tomorrow makes 8 weeks since surgery.  I was told the scar would take months to heal and am patient.  I have a severe curve now, but I haven't measured the degrees.  I'm not entirely displeased because there is less indenture, nearly no hourglass because nearly no indenture on the opposite side, i.e. the circumference is more uniform.  The length is not harmed.  The rigidity is very good and there is not the tendency to buckle anymore.  As I've yet to have intercourse I cannot say how it will function, but I believe it may work fine, although front-to-side positions may be more comfortable.  Financial worries have distracted my attention from obsessing on it, as I certainly was before.  I am one of the nation's sad statistics: over 60 and despite experience, skills, multiple degrees and 3 languages, unemployed.

I'm using my VED once a day under the heat lamp, as heat softens collagen fibers.  (There's a study paper on the application of heat and stretching to tendons followed by chilling, which shows fibers will realign.)  I follow this with an ice cube while bending in the opposite direction.  I'm using vitamin E and Mederma scar cream on the scar.  I don't have great hopes for improvement.  The surgeon said the Buck's fascia and tunica were unaffected, but that he did remove a lot of tissue.  I'll wait another month or two before photographing it again and giving it to James for posting.  It will appear disappointing as it is most certainly worse than in my post-injection photo.  The improvement in curve following the bromelain was temporary.  The improvement in circumference seems permanent.  The VED may help, but I will not be surprised if it does not.

This disease hijacks your mind, commanding your attention; one becomes obsessed with it.  I think that if I'd not been recently divorced and instead been in a relationship with an understanding partner, I would not have become so obsessed.  I could have, and would have, done as my good doctor suggested, "First see if you can have sex comfortably; if not, then we'll talk."  But not knowing if I could have sex again, and not wanting to introduce this problem to a potential partner, I was compelled to go to any lengths to correct it.  I don't regret what I did.  I was desperate, I did a lot of research and I took a calculated risk.  I am indeed improved over the pre-bromelain condition as I had a severe tendency to buckle, so the injections did benefit me, albeit it at a financial and emotional cost.  Still, it beats the cost of Xiaflex, no?

I still think bromelain should be and will be researched.  My surgery was to remove tissue caused, I'm pretty sure, by the Lipoderm, which is meant for topical use.  

I'll post a photo in a month or two.