US5336499A

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United States Patent p19
Antelman

I

5,336,499
Aug. 9, 1994

UU

US005336499A.
Patent Number:

Date of Patent:

(11)
[45]

MOLECULAR CRYSTAL DEVICE FOR
PHARMACEUTICALS

Marvin S. Antelman, Rehovot, Israel

Antelman Technologies, Ltd.,
Providence, R.I.

971,933
Nov. 5, 1992

[54]

[75]
[73]

Inventor:
Assignee:

p21)
[22]

Appl. No.:
Filed:

Related U.S. Application Data
Division of Ser. No. 820,282, Jan. 10, 1992, abandoned.

Int. CLS A61K 7/00
US. Cl. 424/405; 424/618;
424/709; 514/495; 423/604; 210/759: 210/764;
422/19; 422/28

— 424/405, 618, 709;
10/764, 759; 422/28, 19;
514/495

[62]

51]
152]

[58] Field of Search ....

423/604, DIG.

References Cited
U.S. PATENT DOCUMENTS

4,695,353 9/1987
4,717,562 1/1988
4,835,077 5/1989
5,017,295 5/1991
5,073,382 12/1991
5,078,902 1/1992
5,089,248 2/1992

[56]

. 423/604
. 423/604
. 423/604
. 424/618

Jansen et al.
Jansen et al.
Megahed et al.
Antelman
Antelman ..
Antelman
Akhtar .

17
19---C

5,089,275 2/1992 Antelman 424/601

Primary Examiner—Thurman K. Page
Assistant Examiner—Amy Hulina
Attorney, Agent, or Firm—Salter & Michaelson

[57] ABSTRACT

A novel molecular scale device is described which is
bactericidal, fungicidal, viricidal and algicidal. The
anti-pathogenic properties of the device are attributed
to electron activity indigenous to diamagnetic semicon-
ducting crystals of tetrasilver tetroxide (Ag4O4) which
contains two monovalent and two trivalent silver ions
in each molecular crystal. When the crystals are acti-
vated with an oxidizing agent, they release electrons
equivalent to 6.4X 10-19 watts per molecule which in
effect electrocute pathogens. A multitude of these de-
vices are effective at such low concentrations as 0.3
PPM used as preservatives in a variety of formulations
ranging from cosmetics to pharmaceuticals. Indeed,
they are intended as active ingredients for pharmaceuti-
cals formulated to destroy such pathogens as Staphylo-
coccus aureus, and epidermidis, the latter of which it
completely destroys in a nutrient broth culture of about
1 million organisms at 0.6 PPM, or Candida albercans,
the vaginal yeast infection at 2.5 PPM, and the AIDS
virus at 18 PPM.

1 Claim, 1 Drawing Sheet

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Aug. 9, 1994 5,336,499

U.S. Patent

15

1

FIG.

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5,336,499

1

MOLECULAR CRYSTAL DEVICE FOR
PHARMACEUTICALS

This is a division of application Ser. No. 07/820,282
filed Jan. 10, 1992 now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to the employment of
molecular crystals as bactericidal, viricidal and algicidal
devices, but more particularly to the molecular semi-
conductor crystal tetrasilver tetroxide Ag4O4 which has
two trivalent and two monovalent silver atoms per
molecule, and which through this structural configura-
tion enables electronic activity on a molecular scale
capable of killing algae and bacteria via the same mech-
anism as macroscale electron generators. The concept
of molecular scale semiconductor devices for the stor-
age of information has been the subject of much activity
in recent years so that the concept of a molecular scale
device performing such functions as storing information
or acting as resistors, capacitors or photovoltaic devices
is well accepted. The molecular device of this invention
is a multivalent silver diamagnetic semiconductor. Now
the bactericidal activity of soluble divalent silver (Ag
II) complex bactericides is the subject of U.S. Pat. No.
5,017,285 of the present inventor. The inventor has also
been granted U.S. Pat. Nos. 5,078,902, 5,073,382,
5,089,275, and 5,098,582, which all deal with Ag II
bactericides but more particularly with (respectively)
halides, alkaline pH, stabilized complexes and the diva-
Jent oxide. It is the last patent, ie., U.S. Pat. No.
5,098,582, and its perfection that has led to my original
concept of the molecular device of the present inven-
tion. Now said patent designated AgO as divalent silver
oxide, the popular name of the compound. Indeed, the
Merck Index (11th Edition) designates the oxide as
silver(I) oxide (AGO) (entry 8469). However, it also
states that it is actually a silver(I)-silver(II1) oxide with
a molecular weight of 123.88. Said oxide is actually on
a molecular level Ag4O4 where one pair of silver ions in
the molecule is trivalent and another pair is monovalent.

While the formula AgO accurately designates the
silver:oxygen ratio, the molecular weight of the com-
pound is actually 495.52. Further elucidation of the
molecule’s electromagnetic properties reveals that it is a
diamagnetic semiconductor. The structure is electroni-
cally active because of the trivalent sp? electron config-
uration disparity of the electrons within the crystal.

Further testing of the unique oxide was continued on
various types of bacteria, molds, yeasts and algae, be-
yond the water treatment applications claimed in my
previous patents. The phenomenal efficacy of said oxide
against pathogens while they were in constant contact
with their nutrient source in contradistinction to its
efficacy with these same organisms in water, where the
pathogen is separated from a constant nutrient source,
could only be accounted for by considering each mole-
cule of oxide as a “device”. This in turn has led to the
final development of this invention, namely, a molecu-
lar device for killing viruses, fungi, algae and bacteria,
which can be utilized as the active component of phar-
maceuticals and as a preservative against said pathogens
in pharmaceutical and other products.

OBJECTS OF THE INVENTION

The main object of this invention is to provide for a
molecular scale device of a single tetrasilver tetroxide

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semiconductor crystal capable of killing viruses, bac-
teria, fungi and algae when operating in conjunction
with other such devices.

Another object of the invention is to provide for a
molecular device which can be utilized in pharmaceuti-
cals formulated to destroy pathogens.

Still another object of the invention is as a preserva-
tive in pharmaceutical, cosmetic, and related chemical
specialty products against said pathogens.

Other objects and features of the present invention
will become apparent to those skilled in the art when
the present invention is considered in view of the ac-
companying examples. It should, of course, be recog-
nized that the accompanying examples illustrate pre-
ferred embodiments of the present invention and are not
intended as a means of defining the limits and scope of
the present invention.

SUMMARY OF THE INVENTION

This invention relates to a molecular scale device
capable of destroying gram positive and gram negative
bacteria as well as fungi, viruses and algae. Said molecu-
lar scale device consists of a single crystal of tetrasilver
tetroxide. Several hundred thousand trillion of these
devices may be employed in concert for their bacteri-
cidal, fungicidal, and algicidal properties and applied to
industrial cooling towers, swimming pools, hot tubs,
municipal water supplies and various pharmaceutical
formulations.

The molecular crystals which are the subject of this
invention are commercially available and can be pre-
pared by reacting silver nitrate with sodium or potas-
sium peroxydisulfate according to the following equa-
tion: 4AgNO3+2Na2S20¢-+ 8NaOH = A g4O4-4Nap.
SO4+4NaNO3+4H20 The oxide lattice represented
by the formula Ag4Os is depicted in the Drawing FIG.
1. It is a semiconducting electron active diamagnetic
crystal containing two monovalent and two trivalent
silver ions in combination with four oxygen atoms. The
distance between the Ag(HI)—O Ag(I)O units equals
21 A. Ag(I)—Ag(i)=Ag()—Ag()=3.28A and
Ag()—Ag(IID=3.39 A. Each trivalent silver ion is
coordinated via dsp? electron bonds to 4 oxygen atoms.
The depiction of this lattice is based on several litera-
ture references relating to crystallographic studies, Ex-
emplary of this literature are J. A. McMillan’s studies
appearing in Inorganic Chemistry 13,28 (1960); Nature
vol. 195 No. 4841 (1962), and Chemical Reviews 1962,
62,65. Alvin J. Salkind elucidated studies involving
neutron diffraction with his coworkers (J. Ricerca Sci.
30, 1034 1960) proving the Ag(II])/Ag(D nature of this
molecule and states in his classic entitled Alkaline Stor-
age Batteries (Wiley 1969), coauthored with S. Uno
Falk, that the formula is depicted by AgaOu« (page 156).

That same year a scientific communication appeared
in Inorganic Nuclear Chemistry Letters (5,337) authored
by J. Servian and H. Buenafama which maintained that
their neutron diffraction studies also confirmed the
tetroxide lattice and the presence of Ag(IH) and Ag(I)
bonds in the lattice, a conclusion also reported previ-
ously by Naray-Szahn and Argay as a result of their
x-ray diffraction studies (Acta Cryst. 1965, 19,180). Thus
the effects of this invention can be explained in terms of
these structural elucidations, namely, that the single
molecular semiconductor crystal which inevitably must
be electronically active exchanging two electrons per
crystals between its mono and trivalent bonds is in real-
ity a device which kills pathogens in the same manner as

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5,336,499

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electrically active large-scale devices utilized in water
supplies.

When the tetroxide crystals are utilized to destroy
pathogens, they will not do so unless activated by an
oxidizing agent. This is analogous to the behavior of
single semiconducting photovoltaic molecular devices
such as copper indium selenide whose surfaces must be
“etched” in order to activate the photovoltaic activity,
ie., for light to facilitate the release of electrons from
the molecule. The tetroxide was activated by persul-
fates. It was found that when the persulfates were tested
as a control by themselves, they failed to exhibit any
unilateral antipathogenic activity at the optimum level
selected of 10 PPM. The persulfates evaluated varied
from Oxone (Registered Trademark Du Pont Com-
pany) brand potassium monopersulfate to alkali perox-
ydisulfates.

DESCRIPTION OF THE DRAWING

In the drawing which illustrates the best mode pres-
ently contemplated for carrying out the present inven-
tion:

FIG. 1 is a diagrammatic view showing the crystal
lattice of Ag4Oa attacking a pathogenic bacillus.

DESCRIPTION OF THE INVENTION

Turning now to Drawing FIG. 1 depicting the crys-
tal lattice of Ag4Ou, the device operates by transferring
electrons from the monovalent silver ions 10 to the
trivalent silver ions 11 in the crystal 20 through the
aqueous media in Which it is immersed and which con-
ducts electrons depicted by the path 12, contributing to
the death of pathogen 13 with electrons 14, traversing
the cell membrane surface 15, said pathogen being
“electrocuted” by not only these electrons but by oth-
ers: 16 and 17 following paths 18, and 19 emanating
from other molecular devices in the vicinity of the
pathogen. The device is attracted to the cell membrane
surface 15 by powerful covalent bonding forces 21
caused by the well-known affinity of silver to certain
elements present in the membrane, such as sulfur and
nitrogen. Drawing FIG. 1 exaggerates the size of the
silver oxide molecular device with respect to that of a
microorganism for depiction purposes only.

The electron transfer can be depicted by the follow-
ing half reactions in which the monovalent silver ion
loses an electron and the trivalent silver gains one as
follows:

Agt—e=Agt?

Agt3-e=Agt2

The molecular crystal then will become stabilized with
each silver ion having a divalent charge.

Stringent testing was performed in which cultures
were actually placed in trypticase soy nutrient broth,
which allowed the pathogens being tested to replicate
without being detached from its own food supply.
Under these conditions the devices were able to kill two
strains of E. Coli at 2.5 PPM; Micrococcus Luteus at
1.25 PPM; Staphylococcus aureus at 2.5 PPM; Staphy-
lococcus epidermidis at 0.6 PPM; Pseudomonas aerugi-
nosa at 1.25 PPM; and Streptococcus pyogenes at 2.5
PPM.

The devices were then evaluated in analogous nutri-
ent used for yeasts, algae and molds utilizing Sabouraud
dextrose broth. The infectious yeast pathogen Candida

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ALBICANS was totally killed at 2.5 PPM and that of
the Saccharomycetpideae variety at 1.25 PPM.

If we are to consider one molecular device in opera-
tion, then each molecule would release two electrons
having each a charge of 4.8 10-10 e.s.u. equivalent to
approximately 1.6 10—}9 coulombs. The EMF given
in my Encyclopedia of Chemical Electrode Potentials
(Plenum 1982), page 88, for the oxidation of Ag(I) to
Ag(ID is 1.98 volts which approximates 2.0 V. The total
power output per device can be calculated in watts by
multiplying the power output for each electron by 2.
Since power is the product of the potential times the
charge, P=EI; for each electron it would be

2.0X 1.6X 10-19 = 3.2 10~ 19 watts

From this, and using Avogadro’s number, we can calcu-
late that the power flux of one liter of solution contain-
ing 0.5 PPM of devices would be 0.064 watts. Since the
electronic charges of the devices are directly propor-
tional to the number of devices in solution, i.e., the
concentration of the oxide in the solution, we can arbi-
trarily assign our own device power flux constant
which can be used to gauge the concentrations of the
devices required in order to kill particular organisms in
specific environments. I have found the following for-
mula useful for this purpose: Power Flux=EMF gener-
ated per molecule x Concentration x5 (the EMF being
4.0 volts per molecular device; and the concentration is
in PPM). Utilizing this formula, the power flux to effec-
tuate 100% kills for the following organisms is given in
Table I which follows.

TABLE I
Organism Name Power Flux
Escherichia coli 50.0
Staphylococcus aureus 50.0
Streptococcus faecalis 50.0
Streptococcus pyogenes 50.0
Candida albicans 50.0
Pseudomonas aeruginosa 25.0
Micrococcus luteus 25.0
Staphylococcus epidermidis 12.5
EXAMPLE 1

The molecular crystal devices were tested as to
whether they could kill pathogenic microorganisms
with the intent of utilizing them in pharmaceutical ap-
plications. Once it could be determined that the devices
inhibited a particular microorganism, the minimal con-
centration required of the Ag4O4 molecular crystal
devices was determined to inhibit the microorganism in
nutrient broth. One family of pathogens that are known
for their deleterious effects on humans are popularly
called “staph” infections. These infections are com-
monly contracted in hospitals having lax infectious
screening procedures. Accordingly, three staph strains
were Selected as follows for evaluation: Staphylococcus
aureus 9027, 27543 and Staphylococcus epidermidis
12228. The inoculum nutrient broth was prepared ac-
cording to AOAC specifications so as to contain 0.6-1
million organisms per drop of inoculum, each drop
being equal to 0.05 ml. The broth itself was trypticase
soy broth BBL 11766 prepared according to label in-
structions. Accordingly, the broth was prestandardized
for the microorganisms in question in order to assure
that the number of organisms remained constant within
the margins of statistical allowance during the test per-

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5,336,499

5

iod. Having carried out the procedures with 0.05 ml. of
inoculum and having incubated the organisms for 24
hours at 34°-35° C., it was found that staph organism
9027 was inhibited at 2.5 PPM; number 27543 at 5.0
PPM; and the 12228 organism at 0.625 PPM all in the
presence of 10 PPM sodium persulfate. This data was
utilized to formulate a dermatological cream which
would contain 100 PPM sodium persulfate and 10 PPM
of device crystals to inhibit staph infections. The data
was also utilized to formulate a surgical instrument
sterilization formulation and a surgical scrub soap.

EXAMPLE 2

The procedures described in Example 1 were analo-
gously followed for the yeast pathogen Candida ALBI-
CANS using strain 16464 excepting that the nutrient
broth was changed to accommodate this yeast pathogen
to Sabouraud dextrose broth (Difco 038217-9). It was
found that 2.5 PPM of molecular crystal devices com-
pletely inhibited the growth of this gynecological yeast
infection. A gynecological cream and a douche were
formulated against yeasts based on the results, as well as
a cosmetic preservative.

EXAMPLE 3

The devices were tested against AIDS virus. The
protocol used was that of the Ministry of Health of the
State of Israel at their Virology Laboratory located at
Tei HaShomer, Israel. AIDS viruses which had been
grown in vitro in a tissue culture were isolated and
exposed to the devices at device concentrations of 0.05,
1.0, 2.0, 3.0, 5.0 and 10.0 PPM. There was no evidence

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of AIDS suppression at all until the concentrations
reached 5.0 and 10.0 PPM. At 5.0 PPM, 60% of the
viruses were killed. AT 10.0 PPM, 75% of the viruses
were killed. Extrapolation of this data reveals that at
18.0 PPM there would be total suppression of the virus.
These test results indicate that the devices are capable
of being used to destroy viruses in applications involv-
ing the proliferation and transmittal of the AIDS virus
outside of, or for external application on, the human
body as in cold sterilization, or the active component of
chemical specialty lubricants used in condoms.

While there is shown and described herein certain
specific examples embodying the invention, it will be
manifest to those skilled in the art that various modifica-
tions and rearrangements of the invention may be made
without departing from the spirit and scope of the un-
derlying inventive concept and that the same is not
limited to the particular forms herein shown and de-
scribed except insofar as indicated by the scope of the
appended claims.

What is claimed is: .

1. A method of inhibiting the growth of pathogens in
pharmaceutical and cosmetic products, said pathogens
selected from the group consisting of E. coli, Micrococ-
cus Luteus, Staphylococcus aureus, Staphylococcus
epidermidis, Pseudomonas aeruginosa, Streptococcus
pyogenes, Candida Albicans, and Saccharomycet-
pideae, which comprises introducing molecular semi-
conductor crystal devices of the molecule tetrasilver
tetroxide (Ag4Os) in the presence of an oxidizing agent
comprising a persulfate.

*

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