In chemical technology, as in the culinary arts, meerely following a recipe does not ensure success. The yield of any chemical process will vary widely depending on reaction conditions. These include: timing, temperature, air pressure, order of mixing, lighting, etc. Therefore, anyone trying to replicate production of the Koch remedies must appreciate these subtle confounding factors and not give up if initial attempts fail. Running several batches under slightly differing conditions and carefully observing and recording the results will indicate the best methods.
While there exists scarse information from Koch himself about all the idiosyncrasies of how best to produce his remedies his way, there remain copies of patents, notes, letters, exerpts, etc. which are quite informative. The chemical identities of his products prior to dilution were published. For the most part these are commonly available molecules which need not be synthesized. Most can be obtained in suitably pure form (or even in crude form and purified e.g. by sublimation) and then diluted as explained below. If de novo synthesis is preferred, then the details of a variety of methods are readily obtainable from most university libraries which hold references pertaining to organic chemistry. Abstracts, journals, references on synthesis, and organic chemistry texts are commonly available which teach how to synthesize and purify these simple molecules.
Koch made and used the following experimentally or clinically:
Hydroquinone is readily available and can be oxidized by almost any oxidant of medium to high strength (including room air) to produce parabenzoquinone. This can be further purified by sublimation prior to dilution. Similarly hexahydroxybenzene, or tetrahydroxybenzoquinone can be gently oxidized/dehydrogenated to produce rhodozonic acid or triquinoyl (also known as hexaketocyclohexane).
Diphenoquinones can be produced by the oxidative coupling of simple phenols. Upon exposure to a variety of oxidants, monophenols are dehydro- genated to become phenoxyl radicals. These spontaneously couple and tautomerize producing dihydrodiphenoquinones, which upon further oxidation become diphenoquinones.
Glyoxal can be produced by the ozonation of benzene in the presence of water. A mixture of methyl glyoxal and glyoxal results from the ozonation of either toluene or xylene in the presence of water. Ozonides should be prepared under cool conditions and in small quantities to prevent an explosive hazard. Ozonides react with water to produce the desired carbonyl compounds plus hydrogen peroxide. If desired, acid plus zinc powder can be added to remove hydrogen peroxide without destroying the carbonyl products.
There are no published studies by Koch or associates claiming efficacy for diacetyl even though it was present in one of his patents. Diacetyl occurs naturally in butter. It can be synthesized by the dangerous procedure of oxidizing acetaldehyde by hot fuming sulfuric acid. Other safer procedures to produce diacetyl (also known as 2,3-dioxo-n-butane or dimethyl glyoxal) have been published by others long ago.
According to Koch, the most widely applicable and effective catalyst yet found was a mixture of short and long chains of polyketones. This product has variably been called "glyoxylide", the "synthetic survival reagent", the "serial system of carbonyl groups", the "survival factor", etc. Its composition, though plausible from the reactants and conditions used to produce it, has never been confirmed by strict analysis. The best procedure to produce it has similarly been the most difficult to find out. Generally speaking, this mixture was produced by hot fuming sulfuric acid to which a small amount of a polyhydroxy-hydrocarbon such as sugar was added. Catalysis by trace amounts of elemental iodine was mentioned. The sulfuric acid served to dehydrate some of the hydroxyl groups leaving ethylene groups. Room air was slowly bubbled into the mixture as an oxidizing agent. Koch believed diatomic oxygen added to the ethylene groups to produce dioxetanes which would seperate to form carbonyl groups. However the hot oxygen may also have served to dehydrogenate the hydroxyl groups to produce ketones. The final product was expected to be a mixture of oligomers of carbonyl groups conjugated by their adjacent positions, or by ethylene bridges in between them. Chemical Abstracts in its author indices under W.F.Koch lists patents in the U.S., Canada, and Britain describing his procedures. Perhaps simpler and safer methods can be developed in the future to produce mixed oligomers of keto groups using precursors such as glycerine, threitol, sugar, or PEG plus a moderately strong oxidant such as chromic acid.
The Koch catalysts once synthesized were subsequently diluted in pure water, placed within glass viles, and sealed with an oxyacetylene torch. Quinones were diluted to one part per million (one microgram per milliliter) (6X). "Glyoxylide" was diluted to one part per trillion (one picogram per milliliter) (12X). Dilutions in the range of 6X to 10X should be the most practical to work with. 11X or higher would be tedious to manufacture due to instabilities and sensitivities of the catalysts to impurities, light and other destructive factors. Products more concentrated than 6X are unnecessarily strong and irritating to tissues.
Since all of the remedies are composed of conjugated carbonyl compounds, any process must guard against the following:
Dr. Koch strenuously warned that the purity of the aqueous diluent is as or more important than the quality of the mother liquor. It must be free from reductants and nucleophiles. It must not contain substances prown to generate free radicals which might attach covalently to the catalyst, or worse yet initiate polymerization of the catalyst. The pH should probably also be balanced to some optimal level to guard against disproportionation, aldol condensation, or other adverse modifications. Although never reported, the pH was probably slightly acidic. If a less painful injection is desired, the final diluent could be an isotonic salt solution of NaCl, Na2SO4, MgCl2, or MgSO4, provided such can be obtained in suitably pure form. Koch however preferred to use triple distilled water at all stages of dilution. Some tissue irritation at the injection site may hypothetically have been adjunctive to the remedy itself as an immune stimulant. Whether necessary or not, Dr. Koch also succussed the solutions in homeopathic fashion at each stage of dilution. The final product had to be protected from light.
Sterilization of all materials and sterile technique in manufacturing and handling is advised, especially if the final product is to be injected.
Koch used chromic acid to cleanse all glassware, ampuoles, and syringes followed by repeated rinsing with triple distilled water in a pure air lab environment. Ozone gas exposure to the glassware might accomplish the same benefits more easily.
A successful product if taken sublingually will be tasteless at first. Then within a few minutes a slightly astringent (cotton mouth) feeling will be experienced followed by a metallic taste. Many will go on to experience a transient warm flushed feeling several minutes later, and/or feelings of increased pep and mental alertness. Those subjects having allergic symptoms will usually experience relief within a few minutes. If one or more of the above occur, the product should be considered good. The product need not be injected, but can be administered sublingually or by aerosol. If burning, itching, or irritation of mucous membranes is experienced then the concentration is too strong and further dilution is required.
Notice that each of the Koch remedies have several attributes in common being:
Knowing this, it becomes possible to predict that other compounds which can redox cycle might have therapeutic value. Many such compounds indeed have been observed to have beneficial effects similar to those observed in Koch Therapy. Examples are:
If one tries to invent additions to the list of redox cycling remedies, he/she must avoid molecules with bound radicals that could interfere spacially or electrically with the all important redox function. For example, nucleophilic groups shift electrons towards the carbonyl groups and reduce their oxidizing power. Large rings or side chains as in doxorubicin might stereochemically or pharmacokinetically hinder the penetrating ability of the catalyst. Large hydrophobic groups as in ubiquinone or phylloquinone may hinder penetration to or through aqueous spaces. In other words, remedies must not be too lipophobic or too hydrophobic or too bulky or too highly charged to reach and dehydrogenate the appropriate receptors.
Finally it must be advised that in Dr. Koch's experience the success
of his therapy hinged primarily on the degree to which the patient was
properly detoxified and metabolically managed afterwards. The success of
starting a fire is determined more by the dryness of the fuel than by the
brightness of the match. Therefore products which fail clinically could
be misjudged in patients unable to respond due to xenobiotics, toxic bowel,
or other yet to be elucidated hindering factors. Xenobiotics for example
induce the production of enzymes which would be expected to eliminate or
deactivate redox cycling compounds.
Click Here To Peruse The Bibliography Entitled
"Identity And Preparation Of The Koch Catalysts"