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Post by dcassidy1618a on Aug 4, 2016 22:32:52 GMT -5
I just looked and there are studies on sublingual administration of Epinephrine that show postive results. So, yeah, I would guess that a MannKind version would produce effects if I put the powder under my tongue. Would depend on the chemistry required to release the epinephrine from Technosphere. Doesn't seem promising. Inhalation would be better for a conscious person, and injection would be better for an unconscious one. Also consider this quote from Medscape: "The pros and cons of epinephrine administration through various routes are summarized in Table 2. Intramuscular injection into the mid-anterolateral aspect of the thigh is recommended as the initial route of choice in most but not all anaphylaxis guidelines. Epinephrine has a vasodilator effect in skeletal muscle, which facilitates rapid absorption into the central circulation and prompt pharmacologic effects." So a TS-epi could find itself in the same postion as afrezza -- a "non-inferior" alternative to an injection.
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Post by audiomr on Aug 5, 2016 13:50:44 GMT -5
Would depend on the chemistry required to release the epinephrine from Technosphere. Doesn't seem promising. Inhalation would be better for a conscious person, and injection would be better for an unconscious one. It appears that no one actually read what I said. I gave a very likely hypothetical scenario—hiking deep in the woods, no civilization within 60 miles. Your buddy is losing it and there are no options other than breaking the Technosphere-Epi and putting it under his tongue and literally holding his tongue down so it is absorbed sublingually. If you had 5-6 of these it could save his life. I gave you one study do you want another? Some of you have taken me just talking about something that would be a cool additional benefit and have twisted it into something completely different. Do ya'll not ever just talk about stuff without twisting what people say? Not twisting anything. The key question is whether it would work at all. The epinephrine would have to unbind from Technosphere to be absorbed in usable form. I don't know whether that would happen in the mouth. My guess would be that there's a better way to prepare epinephrine for sublingual absorption, in which case your original suggestion (blister packs of TS-epi carried in addition to an inhaler) would not be the way to go. I can understand trying to administer TS-epi that way in your last-ditch deep-woods scenario -- just don't know if there's any actual chance that it would work with that particular formulation of epinephrine. Also don't know how easy or hard it would be to extract the stuff from a Cricket inhaler, which is what presumably would be used for the epi product.
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Post by audiomr on Aug 5, 2016 13:55:19 GMT -5
My comment was related to MannKind being the company to develop what you outline. It does not fit their profile at this time. On a personal note I'd welcome other delivery options for epinephrine. My son has a severe tree nut allergy and carrying around two bulky epi-pens is not ideal. That minor inconvenience is quickly dismissed given the alternative. I'm sure I will be told to consult Hakan for this, but: •TechnoVax, Inc's VLP vaccine technology coupled with MannKind's Technosphere and inhaler technology could make a vaccine for this, IMO. I don't know of any vaccine for any type of allergy. Sometimes it's possible to do long-term desensitization. But vaccines work by priming the immune system to attack specific pathogens. Allergies are an expression of overactive immune response to normally benign stimuli, so the immune system is already primed -- too primed.
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Post by audiomr on Aug 5, 2016 14:00:47 GMT -5
Would depend on the chemistry required to release the epinephrine from Technosphere. Doesn't seem promising. Inhalation would be better for a conscious person, and injection would be better for an unconscious one. Also consider this quote from Medscape: "The pros and cons of epinephrine administration through various routes are summarized in Table 2. Intramuscular injection into the mid-anterolateral aspect of the thigh is recommended as the initial route of choice in most but not all anaphylaxis guidelines. Epinephrine has a vasodilator effect in skeletal muscle, which facilitates rapid absorption into the central circulation and prompt pharmacologic effects." So a TS-epi could find itself in the same postion as afrezza -- a "non-inferior" alternative to an injection. The key benefits of TS-epi would be ease of carrying and ease of administration, which are huge in terms of ensuring that people, children especially, actually get dosed when they need to. Epi-pens are relatively bulky, and it's not easy (again, especially for a child) to inject yourself when you're scared and have to act quickly.
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Post by Deleted on Aug 5, 2016 14:01:50 GMT -5
I'm sure I will be told to consult Hakan for this, but: •TechnoVax, Inc's VLP vaccine technology coupled with MannKind's Technosphere and inhaler technology could make a vaccine for this, IMO. I don't know of any vaccine for any type of allergy. Sometimes it's possible to do long-term desensitization. But vaccines work by priming the immune system to attack specific pathogens. Allergies are an expression of overactive immune response to normally benign stimuli, so the immune system is already primed -- too primed. • INHALABLE VACCINE COMPOSITIONS AND METHODS Type: Application Filed: October 25, 2013 Publication date: October 8, 2015 Inventors: Chad C. Smutney, Andrea Leone-Bay, Jose M. Galarza, Hector Munoz, George R. Martin, Marshall L. Grant — "In one embodiment, dry powder vaccine compositions comprise a diketopiperazine and one or more antigenic components, including virus-like particles (VLPs), immunogenic proteins, peptides or fragments of the viral proteins. In certain embodiments, antigenic molecules which can also be delivered by the methods herein include, antigens derived from pathogenic agents such as parasites, or bacteria, tumor antigens, allergens or self-antigens; or antibodies thereof, can be used to vaccinate or treat against corresponding diseases." patents.justia.com/patent/20150283069#claims
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Post by audiomr on Aug 7, 2016 1:25:43 GMT -5
I don't know of any vaccine for any type of allergy. Sometimes it's possible to do long-term desensitization. But vaccines work by priming the immune system to attack specific pathogens. Allergies are an expression of overactive immune response to normally benign stimuli, so the immune system is already primed -- too primed. • INHALABLE VACCINE COMPOSITIONS AND METHODS Type: Application Filed: October 25, 2013 Publication date: October 8, 2015 Inventors: Chad C. Smutney, Andrea Leone-Bay, Jose M. Galarza, Hector Munoz, George R. Martin, Marshall L. Grant — "In one embodiment, dry powder vaccine compositions comprise a diketopiperazine and one or more antigenic components, including virus-like particles (VLPs), immunogenic proteins, peptides or fragments of the viral proteins. In certain embodiments, antigenic molecules which can also be delivered by the methods herein include, antigens derived from pathogenic agents such as parasites, or bacteria, tumor antigens, allergens or self-antigens; or antibodies thereof, can be used to vaccinate or treat against corresponding diseases." patents.justia.com/patent/20150283069#claimsFact remains, there are no vaccines for allergies. Or at least if there are, I've never heard of them, and I've had various treatments for allergies since I was a child. If such vaccines were possible, Technosphere might be useful for formulating them, but it would not be necessary. One would think some would exist already.
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Post by cm5 on Aug 7, 2016 12:54:11 GMT -5
We all need Technosphere for dry particle inhalation of allergens to induce tolerance to the high risk allergens for which no good/safe/accepted desensitization process currently exists.The major antigens, among others not listed, that are not now safely addressed with existing methods: Peanuts/Nuts Nuts Shellfish Eggs Soy Latex = Natural Rubber Latex: Latex immunotherapy: state of the artAnnals of Allergy, Asthma & Immunology Volume 109, Issue 3, September 2012, Pages 160–165www.sciencedirect.com/science/article/pii/S1081120612005029Update in Pediatric Anaphylaxis A Systematic ReviewBradley E. Chipps, MD1 Capital Allergy & Respiratory Disease Center, Sacramento, CA, USAcpj.sagepub.com/content/early/2013/02/06/0009922812474683.abstractPast, possibly to be experienced again, issues with low quality manufacture of "Natural Latex Rubber" Gloves:FDA Public Health Advisory: Potential Risk of Spontaneous Combustion in Large Quantities of Patient Examination Gloves June 27, 1996 www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062588.htmAnd, too few are aware of this risk:Don't be Misled by "Latex Free" Claimswww.fda.gov/ForConsumers/ConsumerUpdates/ucm342641.htmPowdered Latex Gloves are absolutely associated with asthma and anaphylaxis in HCW (Health Care Workers). There has been stubborn resistance to recognize/correct this issue.
Reasons stated by health care systems, physicians, surgeons, etc are---all too frequently heard include "I like my powdered gloves" "I don't like nitrile/neoprene etc because they are not as easy to put on", and sadly, "the cost is higher", "There's no need to change, it's an overrated issue."
This has continued, despite frequent reports such as just a few examples below:Couriers of asthma: antigenic proteins in natural rubber latex. Petsonk EL National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505-2888, USA.Occupational Medicine (Philadelphia, Pa.) [2000, 15(2):421-430 Dangers of Cornstarch Powder on Medical Gloves: Seeking a SolutionAnnals of Plastic Surgery: July 2009 - Volume 63 - Issue 1 - pp 111-115 doi: 10.1097/SAP.0b013e3181ab43aePresumably, the proposed ban is going into effect, once published in the Federal Register, time to be determined. But----latex sensitivity/anaphylaxis continues to be/will continue to be a health/life hazard, and no safe/effective method of desensitization is currently available.Proposed: Banned Devices; Proposal To Ban Powdered Surgeon’s Gloves, Powdered Patient Examination Gloves, and Absorbable Powder for Lubricating a Surgeon’s GloveComment Period Closed Jun 20 2016, at 11:59 PM ET Note: There is a proposed exception for gloves used during certain radiologic procedures.
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Post by cm5 on Aug 7, 2016 13:55:13 GMT -5
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Post by cm5 on Aug 8, 2016 4:37:29 GMT -5
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Post by audiomr on Aug 8, 2016 12:15:07 GMT -5
We all need Technosphere for dry particle inhalation of allergens to induce tolerance to the high risk allergens for which no good/safe/accepted desensitization process currently exists.The major antigens, among others not listed, that are not now safely addressed with existing methods: Peanuts/Nuts Nuts Shellfish Eggs Soy Latex = Natural Rubber Latex Didn't quote the whole thing just because of length. Anyhow, key word is "desensitization." I underwent a (partially successful) desensitization program for a bee-sting allergy about 50 years ago. This does not involve any sort of vaccine. A vaccine is designed to generate or heighten an immune response to an antigen. This typically involves the administration of one to three standardized dosages over a prescribed period, possibly with additional boosters are relatively long intervals. Desensitization is designed to tamp down an overactive immune response by administering small, gradually increasing doses of the target antigen over a long period of time -- typically weekly over a period of many months, possibly years. Following each dose, the patient must be monitored and his response recorded. There's often a lot of two steps forward one step back. Extreme cases of over-response may require administration of epinephrine to counter anaphylaxis. Nut allergies seem especially difficult, probably at least in part because the quantity required to evoke an extreme response is usually minuscule. It's possible that Technosphere-based desensitization formulations could be useful, but I don't see how they would fundamentally change anything in this realm. They would not automatically be safer or more effective. Might be easier to keep people (children especially) in a program. On the other hand, might be harder to meter the doses with the necessary precision.
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Post by audiomr on Aug 8, 2016 12:19:51 GMT -5
Don't see any reference to inhaled antigens, only inhaled antibodies. Antibodies attack antigens.
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Post by cm5 on Aug 8, 2016 17:54:23 GMT -5
I emphasize "implied" antigens, given the molecular sizes possible now with Technosphere-----size of molecules of antibodies/antigens etc etc not relatively dissimilar.
And, re desensitization 50 years ago-----no comment, other than read current state of the art.
And, desensitization means frequent visits for sometimes a long overarching period of time. And, recipients must wait for varying amounts of time for possible adverse reactions. And, there are uncommon, but known adverse conditions to long courses of sensitizations-----
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Post by cm5 on Aug 23, 2016 7:39:27 GMT -5
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Post by tayl5 on Aug 23, 2016 10:22:02 GMT -5
Does anyone know of any studies where desensitization was used to stop a patient's immune system from attacking the antigens involved in type 1 diabetes?
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Post by audiomr on Aug 23, 2016 10:54:29 GMT -5
Does anyone know of any studies where desensitization was used to stop a patient's immune system from attacking the antigens involved in type 1 diabetes? Don't know how that could be done. Desensitization is normally achieved by exposing a patient to tiny amounts of the triggering agent, starting below the threshold at which a reaction occurs, and gradually ramping up the dose over time so that a tolerance builds up. In autoimmune diseases, some part of the body itself or something it produces is the trigger, so the stimulus is always present and at a level that can't really be controlled.
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