Sherman R.A.,Biotherapeutics, Inc.
Evidence-based Complementary and Alternative Medicine | Year: 2014
Medicinal maggots are believed to have three major mechanisms of action on wounds, brought about chemically and through physical contact: debridement (cleaning of debris), disinfection, and hastened wound healing. Until recently, most of the evidence for these claims was anecdotal; but the past 25 years have seen an increase in the use and study of maggot therapy. Controlled clinical studies are now available, along with laboratory investigations that examine the interaction of maggot and host on a cellular and molecular level. This review was undertaken to extract the salient data, make sense, where possible, of seemingly conflicting evidence, and reexamine our paradigm for maggot-induced wound healing. Clinical and laboratory data strongly support claims of effective and efficient debridement. Clinical evidence for hastened wound healing is meager, but laboratory studies and some small, replicated clinical studies strongly suggest that maggots do promote tissue growth and wound healing, though it is likely only during and shortly after the period when they are present on the wound. The best way to evaluate - and indeed realize - maggot-induced wound healing may be to use medicinal maggots as a "maintenance debridement" modality, applying them beyond the point of gross debridement. © 2014 Ronald A. Sherman.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 148.29K | Year: 2013
DESCRIPTION (provided by applicant): Inflammatory Bowel Disease (IBD), a chronic, recurring disease of the gastrointestinal tract, afflicts over 1.4 million people in the U.S. Curret therapies for IBD are modestly successful and result with significant adverse side effects, including immune suppression and malignancies. Recently, we have identified Lanthionine Synthetase Component C-Like 2 (LANCL2) as a novel therapeutic target and specifically have found that 61610, a compound of the class of bis(benzimidazoyl)terephthalanilides, exerts potent anti-inflammatory activity in mouse models of IBD. The specific aims for the proposed SBIR Phase I are: Aim One will validate LANCL2 as a novel therapeutic target for IBD. Site-specific, atomic-resolution receptor-ligand binding studies will provide the most detailed information related to drug-therapeutic target binding and facilitate a rational design and discovery of novel agonists. Isothermal titration calorimetry (ITC), a label-free thermodynamic technique, and afluorescence-based assay will be used to quantify binding affinity and reaction stoichiometry between LANCL2 and its ligands (i.e., abscisic acid (ABA) and 61610). Previously, our group and others found that ABA binds to LANCL2 and activates cAMP production and activates protein kinase A (PKA). Thus, we will explore downstream effects of administering 61610 on cAMP/PKA signaling. Aim Two will evaluate the efficacy of the bis(benzimidazoyl)terephthalanilides class of anti- inflammatory compounds for treatinggut inflammation. To optimize drug efficacy of bis(benzimidazoyl)terephthalanilides for anti-inflammatory effects in IBD, we will (1) generate 20-50 derivatives and analogs of 61610, (2) perform compound screening based on LANCL2 binding, cAMP/PKA signaling and exclusion of PPAR gamma activation to select 3 lead derivatives/analogs for further development in vivo, and (3) compare the oral administration efficacy of 3 lead compounds against the parent compound 61610 and prednisolone, a steroid used by IBD patients, in mouse models of IBD. SBIR Phase II will optimize two of the lead compounds with demonstrated efficacy in mouse model of gut inflammation and advance them along the regulatory pathway, including efficacy, mode of action, absorption, distribution, metabolism and excretion (ADME), phamacokinetics/pharmacodynamics (PK/PD), toxicokinetics (TK) analysis and toxicity assessment working towards the testing required to submit an investigational new drug (IND) application in preparation for human clinicaltrials. To optimize drug delivery in the gut we will develop more water-soluble 61610-based pro-drugs and test their efficacy and safety. Long Term Goal: For moderate to severe cases of IBD, the goal of BioTherapeutics technology will be to provide an oral therapeutic alternative to existing treatments that costs less and provides greater efficacy with reduced adverse side effects. The technology will address the overlying health problem with patients suffering with IBD and will provide a significant commercialization potential estimated to be over 800M. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Inflammatory bowel disease (IBD) afflicts over 1.4 million people in the United States with a worldwide prevalence reaching up to 396/100,000 persons. This Phase I SBIR will develop a novel class of potent anti- inflammatory drugs for IBD. The proposed feasibility studies will lay the groundwork for creating new chemical entities and discovering how bis(benzimidazoyl)terephthalanilides modulate immune and inflammatory responses in humans.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 188.33K | Year: 2013
DESCRIPTION (provided by applicant): About 28.3 million Americans have type II diabetes (T2D) and over 40.1% of middle-aged adults have prediabetes, a condition characterized by impaired glucose tolerance and insulin resistance. Current antidiabetic medications are effective in improving insulin sensitivity, but their chronic administration has significant side effects suc as cardiovascular complications, hepatotoxicity, adipose tissue accumulation, and fluid retention, bladder tumors. We have discovered anaturally occurring isoprenoid, abscisic acid (ABA) that increases insulin sensitivity and suppresses inflammation in overweight and obesity. Recently, we have identified Lanthionine Synthetase Component C-Like 2 (LANCL2) as a novel molecular target for ABA. This project will evaluate the efficacy and safety of novel ABA derivatives for treating diabetes. The specific aims for the proposed STTR Phase I are: (1) To generate 20 derivatives and analogs of ABA for development of diabetes and obesity-related inflammation drugs; (2) To perform in silico and in vitro screening to select lead derivatives for further development; and (3) To compare the oral efficacy of ABA-derived drugs against pioglitazone, an approved diabetes drug, in two mouse models of diabetes.At the conclusion of this effort our team will have identified two derivatives of ABA that have undergone extensive in vitro testing and are safe and with proven efficacy in two mouse models of diabetes. We will have filed at least one patent applicationwith robust composition of matter claims for the new class of anti-diabetic drugs that target the LANCL2 pathway. The proposed studies will differentiate the mode of action (MOA) of ABA and its new derivatives from binding to peroxisome proliferator-activated receptor g. This work will provide an excellent assessment of the feasibility of developing novel ABA-based treatments for diabetes. STTR Phase II will optimize two of the lead compounds with demonstrated efficacy in mouse models of diabetes and advance them along the regulatory pathway, including efficacy, mode of action, absorption, distribution, metabolism and excretion, phamacokinetics/pharmacodynamics, toxicokinetics analysis and toxicity assessment working towards the testing required to submit aninvestigational new drug application in preparation for human clinical trials. To optimize oral drug delivery we shall develop more analogs that have molecular properties (ClogP, molecular weight, polar surface area, numbers of rings, rotable bonds, N andO atoms, hydrogen bond donors and acceptors) within the guidelines; and test their efficacy and safety. Long Term Goal: The goal of BioTherapeutics (BTI) technology will be to provide an oral therapeutic alternative to existing diabetes treatments that costs less and provides greater efficacy with reduced adverse side effects. The technology will address the overlying health problem with patients suffering with diabetes and will provide a significant commercialization potential to a market of 28.3 millionestimated to be over 12.5 Billion for prescription medication costs alone annually in the US. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Abscisic acid has demonstrated efficacy in ameliorating diabetes and obesity-related inflammation. The studies will develop a new class of safer and more efficacious diabetes drugs. Thus, the proposed STTR application is timely and important because it will help to develop superior treatments for diabetes, a disease that afflicts almost 30 million Americans.
Biotherapeutics, Inc. | Date: 2014-01-08
The present invention relates to a cryopreservative device comprising an outer case, one or more layers of space for the cryo-bags, and two or more Teflon cryopreservative bags. The outer case has a cover lip for opening and closing. The Teflon cryopreservative bags are filled with a freezing resistant. In the present invention, the cryo-bags and the Teflon cryopreservative bags are crossly stacked in the cryopreservation device. The Teflon cryopreservative bags are designed to directly contact with the cryo-bags in order to obtain the effect of slow cell freezing.
Biotherapeutics, Inc. | Date: 2015-03-19
Provided are compounds that target the lanthionine synthetase C-like protein 2 pathway. The compounds can be used to treat a number of conditions, including infectious disease, autoimmune disease, diabetes, and a chronic inflammatory disease.