02/21/2021
Business plan to raise capital for Pointcare Systems, Inc. DBA Chirosolve, Inc.
San Jose, CA. 95123 USA.
Tel # 1-408-391-9735
Our Aim is to raise USD 17.5M in exchange for equity offerings or loan or combination of several financial instruments/scenerios.
Pointcare Systems has following activities:
A) Point-of-care assay for Homocysteine (exit strategy-out license) Require 1.5M-USA based
Currently, there are commercial and hospital laboratories which are performing homocysteine tests using the above described method. But there are many drawbacks associated with this solution:
Since the tests require the use of high cost equipment and require specially skilled staff to do the tests, the cost of these tests is high(upto$100/-per unit)
The tests require large volume of blood sample(8cc) and the sample has to be transported to the central laboratory. It can take upto a week to get the results back
High homocysteine level is not an immediate life threatening symptom.Therefore many times,the follow-up consultation required to discuss the results with the patient gets overlooked
Due to all these factors, today these tests are only ordered for high risk patients and are not utilized as standard practice. Additionally, since homocysteine measurement is not available through currently available panels, ordering this test separately significantly increases the total cost of cardiovascular profiling.
The goal of this project is to develop technology suitable for simple point-of-care (POC) detection and determination of homocysteine. Advantages of this solution are:
CLIA waived test needing minimal FDA approval
Does not require specially trained staff either to draw the blood or to do the test
Needs only few drops of whole blood
Test done in doctor’s office, results in15minutes
(1)Point-of-care assay for Folates/Folic acid vitamin B-6 (exit strategy out license) Require 1.5M-USA based
The global burden of folate insufficiency as it relates to NTDs has not yet been determined, but is estimated to be over 200,000 pregnancies yearly. This gap in data is primarily because large-scale national surveillance studies of folate levels and NTDs have not been possible in many countries. Additionally, many countries have remote areas where access to appropriate laboratory facilities is limited or available laboratories have limited capacity for biological testing. An assay that can add data on folate status from remote areas to a country’s surveillance system can allow for an accurate burden of disease estimate. Development of these new assays would provide the means to document the folate status of target populations and help determine a course of action to address folate insufficiency programmatically. The expectation is that the proposed technology will meet market demand by laboratories and in-the-field research groups.
There are several assays exist that includes but not limited to microbiological assay, ninhydrin color tests as well as spectrophotometric assay that describes in analytical biochemistry journal that uses color tests. But as of to-day none of these test are Point-of-care test that can be performed at the doctor’s office/bedside.
(2) Chirosolve has following activities:
1) Manufacture and sale chirosolv kits for world-wide markets through distributors as well selling directly. Presently we manufacture in the USA but we could do it India. (min.1.5M for effective sales/marketing efforts).
Chirosolve continually looking to improve their product line such as Strong acid kits-number of pharmaceuticals/API are weak bases and they do need strong acids to form salts so that pharma molecules can be resolved, therefore recently we introduce strong acid kits from our existing resolving agent inventory. Sometimes, few research groups like to introduce their new resolving agents through chirosolv kits (chirsolve can be great marketing tool for theirnew product). After examining resolving power of these new agents-chirosolve take initiative to introduce exclusive kits.
Last year, we have introduced “Enantioprep” (complimentary to chiral chromatography-please check our website for more info.& “Scale-prep” kits as well.
2) Develop “Green Kits” based on Co-crystallization- Require Co-Crystal technology: 1.5M
It means crystals with more than one kind of molecule. The basic concept behind a co-crystals are thus distinct from salts which comprise separate anions and cations because it is impossible to separate a salt into the pure anions and pure cations-electrostaic charge balance consideration means that each ion must always be partnered by an oppositely charged counter-ion. This is not the case for co-crystals where the different molecules found together in the crystals are distinct, separate and separable chemical substances. The pseudopolymorphs, hydrates, solvates and all solid-state host guest compounds are examples of co-crystals. As with polymorphism, co-crystals are of considerable interest within pharmaceutical industry. There is thus a great deal of interest in distinguishing between co-crystal of a neutral base such as phenethyl amine and neutral acidic molecule such as tartaric acid,and salt formed by proton transfer from the acid to amine. The distinction between salt and co-crystal here essentially revolves around the movement of a single proton and thus a crystal of a particular such acid/base compound may be a salt at one temperature and a co-crystal at another! Consequently any crystal with more than one separable molecular component may be thought of as a co-crystal. A particularly common and interesting kind of co-crystal is one in which two enatiomers of the same chiral molecule co-crystallise to give a racemic crystal. Because enantiomers commonly do not interconvert in solution under conditions (usually high energy covalent bond breaking and re-forming is required) then a crystal of two enantiomers is formally a co-crystal. A simple example of designer co-crystal comes from the combination of alcohols with amines. An alcohol may be regarded as ideally donating one hydrogen bond and accepting two (one for each lone pair), while an amine is perfectly complementary to it, donating two hydrogen bonds and accepting one. Furthermore, alcohols are generally Bronstead acids, and amines are bases, so there is a high degree of mutual affinity. Statistical analysis for the existing co-crystals suggests that acid, amine & water are most commonly occurring motifs. And these three components are at the heart of chirosolv’s kits.
The goal of this project is to 1) replace amine as resolving agent for acids in few cases wherever it is possible And 2)use of non-toxic/non-volatile solvent or even solventless reactions. For the first objective Only way you could achieve that by examining Co-crystallization technology such as acid-acid acid-amide, acid-heterocycle interactions. The prominent example of optical resolution on a commercial scale that appears to rely on co-crystal complex formation is Pfizer’s block buster drug Pregabalin (Lyrica) for the treatment of fibromyalgia. In the original resolution α-methylphenethyl amine was used to resolve β-amino acid (Lyrica) which was replaced by mandelic acid (50-100% excess), that form complexes with Pregabalin in aq. Propanol. Two crystallizations in the presence of additional mandelic acid produces material with 99% (ee) and 70% yield.
3) Develop “Green Kits” based on Chiral ionic liquids-Require 1.5M
Chiral ionic liquids are recently being explored, especially interesting are directly derived/synthesized from the “Chiral pool” (amino acids, hydroxyl acids, amines, aminoalcohols, terpenes and alkaloids). They are used in asymmetric synthesis, enzymatic chemistry, chiral chromatography).
Room temperature ionic liquid (ILS) have attracted much recent interest as novel solvents and electrolytes for chemical and electrochemical synthesis, catalysis, and battery applications because of their remarkable properties such as high ionic conductivity, wide electrochemical potential window, low volatility, good chemical and thermal stability, and ability to dissolve a wide range of organic and inorganic species. These properties have led them to being championed as “ Green Solvents” for range of chemical processes.
We now know that a variety of RTILs can be synthesized and that they are generally consist of organic salts or mixtures of an organic ion plus a relatively large, often poorly coordinating inorganic ion.
We are specially interested in developing application in chiral separation from the racemic mixture and that is our core competence. As we are chirosolve a chiral separation company involve in manufacturing chirsolv-chiral kits for last three/four years. At present we use chiral acids and amines in our kits with organic solvents and we would like to explore the possibility of using chiral ionic liquids in kit format that could be used to resolve racemic mixture. Here advantage would be chiral ionic liquid act as resolving agent and solvent.
Perform services for purely on racemate resolution can be perform the USA or in India. (Already established) depending upon customer demands-few will insist to perform these services in the USA.
5) Other custom services as demanded by market such as reference compounds (biphthalates, monophthalates, metabolites (API’s), Stable-isotope labeling, chiral insectides such as pesticides ( pyrethrins etc) can be done in USA or India (If funded by the US government grants then work must be done in the USA). Our company also would be examining racemic drugs as possible chiral/racemic switches (drug development project).
API manufacturing:
Establish manufacturing unit in India (existing unit) for chiral intermediates (Chirosolve posses Know-How for over ‘sixty products’ kept it as trade secrets/ manufacturing API(we have technology Know-How for more than 200 products) in near future--start with non-GMP facility to begin with.
Set it up as generic drug manufacturing facilities in India.
Requirements-5M-10M
Some of the key importance of chirality (usage of chiralty in speciality chemicals): Relationship between absolute configuration and biological activity of enantiomerically related compounds (reference book-Mirror-Image Asymmetry by James P. Riehl, 2010):
Serial # Name of Compound Absolute Configuration Biological effect
1 Asparagine R Sweet taste
S Bitter taste
2 Carvone R Spearmint flavor
S Caraway Flavor
3 1-Chloropropane-2,3-diol R Toxic
S Antifertility activity
4 Thalidomide R Sedative,hypnotic
S Extream teratogen
5 Propanolol R Contraceptive/130 fold stronger
S Antihypertensive, Antiarrhythmic
6 Levodopa R Toxic
S Treatment for Parkinsonism
7 Naproxen R Liver Toxin
S Anti-inflammatory
8 Ibuprofen(Advil) R Inactive
S Anti-inflammatory
9 Chloramphenicol R,R Antibacterial
S,S Inactive
10 Ethambutol R,R Causes blindness
S,S Tuberculostatic
11 Paclobutrazol R,R Fungicide
S,S Plant growth regulator
12 Deltamethrin R,R,S Potent insecticide
S,S,R Inactive
13 Fluazifop butyl R Herbicide
S Inactive
14 Penicillamin R Toxic
S Antiarthritic
15 Lemonene R Orange odor(termite killer)
S Lemon odor
16 Warfarin Hypoprothrombinaemic; (S) 5-6 times more potent than (R)
17 Dexetimide S Muscarinic acetylcholine receptor affinity-10,000 fold stronger than
Levetimide R Weaker affinity
18 Darvon 2R,3S analgesic
Novrad 2S,3R antitussive
Top nine out of ten selling drugs are chiral such as Lipitor, Plavix etc.
We posses know-How “sixty” products (huge IP), we could also provide know-how for food ingredient such as Menthol, non-nutritional sweetner Aspartame-nutrasweet, agriculture product metachlor, phenoxypropionic acid-herbicide, pyrethroids-insecticide, Naproxen, Ibuprofen (advil), D-Proline etc.
