Haha, pretty crazy, it is not even allowed to *ship* topical papain solutions

In efforts to ensure the safety and efficacy of prescription medications, the Food and Drug Administration (FDA) is taking action to remove unapproved products from the market, specifically topical papain.1 Some of the topical papain products include Accuzyme, Ethezyme, Kovia, Panafil, and Ziox. These products are commonly used to treat pressure ulcers and other wounds. Companies must stop manufacturing unapproved topical papain products by November 24, 2008. Also, the shipment of these products must stop by January 21, 2009.

Background
Papain is a proteolytic enzyme isolated from papaya fruit (Carica papaya).1 It is used as an enzymatic debridement to degrade necrotic tissue found in wounds. Papain is combined with urea to enhance its debridement activity.2 Some papain-urea formulations contain a chlorophyllin-copper complex, which acts as a deodorizer and may also have mild antiinflammatory properties. Although topical papain products are widely used in wound care, these products are associated with causing serious hypersensitivity reactions that may result in cardiovascular symptoms (hypotension and/or tachycardia), require emergency room visits, or require treatment with epinephrine.1 In addition, there are reports of patients with a latex allergy experiencing cross-sensitivity to certain fruits, such as papaya. Due to these products not being FDA-approved and safety concerns, they are being removed from the market. Manufacturers will have to submit a new drug application (NDA) or an abbreviated NDA to the FDA in order to market topical papain products. Currently, no company has issued a press release regarding the submission of an NDA.3-6

The rest of this article,, with some pointers for possible alternatives.

What are alternatives to topical papain for wound care?

Introduction
In efforts to ensure the safety and efficacy of prescription medications, the Food and Drug Administration (FDA) is taking action to remove unapproved products from the market, specifically topical papain.1 Some of the topical papain products include Accuzyme, Ethezyme, Kovia, Panafil, and Ziox. These products are commonly used to treat pressure ulcers and other wounds. Companies must stop manufacturing unapproved topical papain products by November 24, 2008. Also, the shipment of these products must stop by January 21, 2009.

Background
Papain is a proteolytic enzyme isolated from papaya fruit (Carica papaya).1 It is used as an enzymatic debridement to degrade necrotic tissue found in wounds. Papain is combined with urea to enhance its debridement activity.2 Some papain-urea formulations contain a chlorophyllin-copper complex, which acts as a deodorizer and may also have mild antiinflammatory properties. Although topical papain products are widely used in wound care, these products are associated with causing serious hypersensitivity reactions that may result in cardiovascular symptoms (hypotension and/or tachycardia), require emergency room visits, or require treatment with epinephrine.1 In addition, there are reports of patients with a latex allergy experiencing cross-sensitivity to certain fruits, such as papaya. Due to these products not being FDA-approved and safety concerns, they are being removed from the market. Manufacturers will have to submit a new drug application (NDA) or an abbreviated NDA to the FDA in order to market topical papain products. Currently, no company has issued a press release regarding the submission of an NDA.3-6

Wound bed preparation
The process of converting a chronic wound into a healing wound is referred to as wound bed preparation.7 Wound bed preparation emphasizes the removal of barriers by applying the TIME principles: every wound should be assessed for nonviable or deficient tissue, inflammation or infection, moisture imbalance, and a non-advancing or undermined wound edge.8 Debridement, the removal of nonviable tissue, is a widely used tool in wound bed preparation. There are several debridement techniques: surgical (sharp), mechanical, autolysis, chemical (enzymatic), and biological (maggot therapy). The type and volume of necrotic tissue, the presence of underlying infection, wound size, pain associated with the technique, presence of comorbid conditions (i.e. sepsis), vascularity of the wound and adjacent tissue, patient preference, and cost are factors that influence the selection of a debridement technique.9

Available Alternatives
Enzymatic debridement is frequently used alone or in combination with other techniques.9 Currently, there are 3 types of enzymatic agents available: papain-urea (with or without chlorophyllin), collagenase, and trypsin/castor oil/Peru balsam.8 However, due to the FDA’s mandate, topical papain products are being removed from the market.1 In a statement by the FDA, collagenase and becaplermin are recommended as approved topical alternatives that are effective in treating various types of wounds.1 Trypsin/castor oil/Peru balsam is an additional alternative.8

Collagenase (Santyl), derived from Clostridium histolyticum, is an enzyme that digests collagen fibers that attach nonviable tissue to the wound.2 Santyl ointment is the only marketed collagenase product, and the only debriding agent covered by Medicare.10 It is indicated for debriding chronic dermal ulcers and burn areas.11 Collagenase has an active pH range of 6 to 8. Higher or lower pH conditions will decrease the enzyme’s activity. Also, certain detergents and soaks containing heavy metals (silver or mercury) or acidic solutions should be avoided as they affect the enzyme’s activity. Cleaning materials such as hydrogen peroxide, Dakin’s solution, and normal saline can be used with Santyl. The ointment should be applied once daily, and discontinued when the necrotic tissue is completely debrided and granulation tissue is well established. A slight transient erythema to the surrounding tissue has been occasionally noted. Unlike papain, collagenase works from the “bottom up” by selectively degrading collagen anchored to the wound.2 In a systematic review, Ramundo and colleagues found evidence that collagenase removed necrotic tissue more rapidly from the wound than placebo.9 In a randomized, prospective, comparative trial of 26 patients with pressure ulcers requiring debridement, papain-urea (Accuzyme) removed necrotic tissue from the wound at a faster rate than Santyl.12 However, there was no significant difference in the healing rates and overall condition of the wounds between the 2 groups.

Becaplermin (Regranex Gel) is a topical recombinant human platelet-derived growth factor (rh-PDGF) indicated for the treatment of lower extremity diabetic neuropathic ulcers.13 Its activity is similar to the biological activity of platelet growth factors such that cellular proliferation and granulation tissue formation are enhanced. Regranex Gel should be applied once daily until the ulcer has completely healed. The probability of complete healing is increased when becaplermin is used as adjunct therapy to good wound care practices (initial sharp debridement, pressure relief, and infection control). There is evidence that demonstrated becaplermin to be effective in treating pressure ulcers.14 In a multicenter, double-blinded, placebo-controlled trial of 124 patients with pressure ulcers, becaplermin had a significantly greater effect on complete healing than placebo after 16 weeks of treatment or complete wound healing, whichever came first.

Trypsin is an endopeptidase with mild debridement activity.8 It is formulated with castor oil, and Peru balsam.15 This combination product is indicated for wound healing pressure ulcers, varicose ulcers, and dehiscent wounds. It is supplied an ointment (Xenaderm), spray (Granul-Derm), and gel (Optase). The pH range required for activity is 3 to 12.8 Avoid using agents that contain silver as they can reduce the efficacy of the trypsin combination.10 In small studies trypsin increased blood flow, enhanced re-epithelialization, and reduced edema in wounds.8 However, larger studies are needed to better evaluate the efficacy and safety of trypsin in chronic wounds.

Conclusion
Chronic wounds are difficult to heal, and the process may take a long time. An advantage of enzymatic debridement agents is their ability to reduce healing time. However, there is no agent is preferred over another. Due to the removal of papain products from the market, other topical debridement agents are being considered for wound bed preparation. There are 3 alternatives available: collagenase, trypsin, and becaplermin. When selecting an agent, consider the TIME principles and the best agent for the wound and patient.

References

1. Food and Drug Administration. Questions and answers about FDA’s enforcement action regarding unapproved topical drug products containing papain. Available at http://www.fda.gov/cder/news/papain/qa.htm. Accessed October 8, 2008.
2. Kravitz SR, McGuire J, Zinszer K. Management of skin ulcers: Understanding the mechanism and selection of enzymatic debriding agents. Adv Skin Wound Care. 2008;21(2):72-74.
3. Allan Pharmaceutical. Available at http://www.allanpharmaceutical.com/. Accessed October 29, 2008.
4. Healthpoint, Ltd. Available at http://www.healthpoint.com/news.cfm. Accessed October 29, 2008.
5. Onset Therapeutics. Available at http://www.onsettx.com/press.html. Accessed October 29, 2008.
6. Stratus Pharmaceuticals, Inc. Available at http://www.stratuspharmaceuticals.com/pages/news6.html. Accessed October 29, 2008.
7. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: A systematic approach to wound management. Wound Rep Reg. 2003;11(Suppl 1):S1-S28.
8. Falabella AF. Debridement and wound bed preparation. Dermatologic Therapy. 2006;19(6):317-325.
9. Ramundo J, Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs. 2008;35(3):273-280.
10. Comparison of chronic wound care products. Pharmacist’s Letter. 2008;24(5):240511.
11. Santyl [package insert]. Fort Worth, TX: Healthpoint, Ltd; 2007.
12. Alvarez OM, Fernandez-Obregon A, Rogers RS, et al. A prospective, randomized, comparative study of collagenase and papain-urea for pressure ulcer debridement. Wounds. 2002:14(:293-301.
13. Regranex Gel [package insert]. Raritan, NJ: Ortho-McNeil-Janssen Pharmaceuticals, Inc.; 2008.
14. Rees RS, Robson MC, Smiell JM. Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study. Wound Rep Reg. 1999;7(3):141-147.
15. Castor Oil/Peru Balsam/Trypsin. Micromedex Healthcare Series [internet database]. Greenwood Village, CO: Thomson Healthcare. Updated periodically.

i dont know much about it, but it wouldnt suprise me if the fda new they were gonna lose alot of money if a free hairloss cure was finally available. So they would do this to stop it ever happenening. thoughts?

cue - Perhaps. Everything is possible. We all know the lobby of the drug companies.
But on the other hand, you can't deny all the physical facts and properties of papain. that can be dangerous on different circumstances...
Since only 2 years on this forum, i'm sure few peoples here knew how to stop their hairloss. Different ways.
And there are still no magic bulet.

europe, some (lucky?) people lasers seem to be a magic bullet .. Dont you have a hefty laser helmet with how many diodes, and what is your impression, is it effective?

I'm not sure about my laser helmet but since I only have 100+ diodes maybe it is too few ..?

What i wanted to say about papain, is yeah, that deserve a GO ! But for 2 years here, i've seen so many "GO" that ended up with a "STOP".
So yeah, papin would be helpful, but be careful here, with on the top of that different serious applications of topical papain. I'm gonna make a go for that papain powder.

But once again, i'm a jerk off. I mean, i started laser 300 helmet OMG 2 in may 09, and had good results so far. Since 3 weeks ( 4-5 months) i experienced a shedding. But the overall seems still good and the one that are left seem thicker, healthier. So i see that shed as a good sign.
But i started lugols, re started curcum and resve . It sucks, i MUST wait 3-4 months between each.
And what i wanna do now is to add papain....

Wel, we'll see...but i would recommend everyone to use the laser helmet. Definitly a must for me. I want to add that i used for years a lasercomb. A disaster. At least, that helmet isn't a pain in the ass, and it's really important to be consistance in time...

By the way, speaking of papain, is it compatible with :

1) lasers with mag oil
2) Topical L-lysine. Because it seems jdp had a really good impression.

Speaking of the magic bullet, and as prague stated, he takes other things and above all he had a SPECIFIC regimen that can be part of his success story.
Hopefully, i have the same regimen as him, same philosophy at least, so i'll definitly try that papain mix in fex weeks, and report to you bros.

Cheers