F O R M 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. TITLE OF THE INVENTION: – HERBO-MINERAL PREPARATION /
MEDICINE TO IMPROVE IMMUNITY
2. APPLICANT:
a) NAME
b) NATIONALITY
c) ADDRESS : Shripad Medi-Search Pvt Ltd : Indian Company
: 32/2A, Erandwane, Gulwani Maharaj Road, Pune 411004, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which
it is to be performed.

HERBO-MINERAL PREPARATION / MEDICINE TO IMPROVE IMMUNITY
Field Of The Invention
The invention relates to a heromineral composition having at least 10 active herbomineral ingredients. The invention covers 7 herbal medicines and 3 minerals or 8 herbal medicines and 2 minerals or 9 herbal medicines and 1 – 2 minerals.
Object of the invention
The object of the invention is to provide a single composition having at least 10
herbomineral ingredients, preferably 11 – 12 herbomineral ingredients for
immunomodulatory action to enhance immunity in general and to enhance
immunity in people vaccinated with covid vaccine such as covaxin.
The rasayana herbal medicines are preferably in the form of ‘Ghan’ and minerals
are preferably in the form of ‘Bhasma’ or in ‘Colloidal’ or in ‘Nano particulate’
form.
Summary of the invention
Under the first aspect, invention provides at least 10 herbomineral ingtredients, preferably 11 – 12 herbomineral ingredients to improve immunity as immunity modulator. At least 8, preferably 9 or 10 herbal medicines and at least 1 – 2 minerals are combined. The rasayana herbal medicines are preferably in the form of ‘Ghan’ and minerals are preferably in the form of ‘Bhasma’ or in ‘Colloidal’ or in ‘Nano particulate’ form. The compositions are immunomodulatory in action to enhance immunity in general and to enhance immunity in people vaccinated with covid vaccine such as covaxin.
Brief Description of Drawings
Figures 1 – 3 provide preparation of Ghan by aqueous / water extract or by super critical extraction
Figure 4(a): EDS report identify and characterize the elemental composition of Cap IP. Elements identified are Calcium (ca), Zinc (Zn), Magnesium (Mg), Silicon (Si) and In.

Figure 4(b): EDS Report of Zinc (Zn) in the composition.
Figure 4(c): EDS Report of Calcium (Ca) in the composition.
Figure 4(d): EDS Report of Magnesium (Mg) in the composition.
Figure 4(e): EDS Report of Silicon (Si) in the composition.
Figure 4(f): Particle Size of the composition (ranges approximately 14 -29nm.)
Figure 4(g) and 1(h): Graphical and Tabular representation of spectrum data for
the percentage of elements present in the composition.
Figure 5(a): EDS report identify and characterize the elemental composition of
Cap IP. Elements identified are Calcium (ca), Zinc (Zn), Magnesium (Mg) and
Silicon (Si). Figure 5(b): EDS Report of Silica (Si) in the composition.
Figure 5(c): EDS Report of Calcium (Ca) in the composition.
Figure 5(d): EDS Report of Magnesium (Mg) in the composition.
Figure 5(e): EDS Report of Zinc (Zn) in the composition.
Figure 5(f): Particle Size of the composition (ranges approximately 12 -27nm.)
Figure 5(g) and 5(h): Graphical and Tabular representation of spectrum data for
the percentage of elements present in the composition.
Background Of The Invention
Recent time is marked with a Coronavirus pandemic which is a threat to entire humanity. In absence of any vaccine, and medication that can effectively tackle all mutants and all stages of the virus, the larger emphasis is placed on immunity of the individual. Older population having low immunity is at higher risk than ever before. India’s older population (age 60 and above) is projected to climb from 8 % in 2010 to 19 % in 2050. This population should be disease and disability free with high physical and cognitive function and active engagement with life. This is possible with enhancement in immunity.
Immunity may be defined as the body’s ability to identify and resist large numbers of infectious and potentially harmful microorganisms, enabling the body to prevent or resist diseases and inhibit organ and tissue damage. Immunity also plays a vital role in maintaining health and prolongs the ageing process. It also plays important role in fighting dreadful diseases like cancer etc.

The immune system is not confined to any one part of the body. The immune system is made up of special organs, cells and chemicals that fight infection (virus, bacteria, fungi etc.). The main parts of the immune system are: white blood cells, antibodies, the complement system, the lymphatic system, the spleen, the thymus, and the bone marrow. These are the parts of your immune system that actively fight infection. The immune system keeps a record of every microbe it has ever defeated, in types of white blood cells (B- and T-lymphocytes) known as memory cells. This means it can recognise and destroy the microbe quickly if it enters the body again, before it can multiply and make you feel sick.
Some infections, like the flu and the common cold, have to be fought many times because so many different viruses or strains of the same type of virus can cause these illnesses. Strong Immunity is the Defense to Protect from many infections including Viral infection (e.g.Corona). Immune stem cells, formed in the bone marrow, may remain in the bone marrow until maturation or migrate to different body sites for maturation. Subsequently, most immune cells circulate throughout the body, exerting specific effects. The immune system has two distinct but overlapping mechanisms with which to fight invading organisms, the antibody-mediated defense system (humoral immunity) and the cell-mediated defense system (cellular immunity). Nature has been an excellent source of therapeutic agents since the time immemorial. Traditional and conventional medicines are mostly based on numerous natural resources, including plants which are being used as a primary source in folkloric medicine. Before the discovery of chemical and synthetic compounds, these plants played a significant role as a traditional medicine for curing various diseases throughout the world. However, with the emergence of modern techniques and equipment, synthesis of new classes of synthetic compounds has attracted attention among researchers during recent years. Some of these compounds were first isolated from the natural sources but further modified to improve their efficacy

Detailed description of the invention
The words preparation and compositions are used synonymously.
The invention provides an immunomodulatory composition of herbomineral ingredients.
It enhances general immunity.
It enhances immunity in people who have taken Covaxin dose thereby enhances immunogenicity against Covid 19.
It enhances immunity in people who have taken vaccine against any other viral infection.
The present invention provides in a single dosage form in reduced dosage, at least 10 – 12 herbomineral ingredients with medicinal properties like antiviral, anti-inflammatory, analgesic, immunomodulatory, antioxidant etc.
Synergic effect of these ingredients can act as immunomodulator in individuals. Particularly when immunity is desired in the present time due to outbreak of Covid-19 pandemic. The immunomodulatory composition of the present invention is therefore tried in subjects who have received 2 doses of Covaxin. After receiving Covaxin to generate immunogenicity against Covid 19, subject will have 100 % antibodies against the Covid 19 for period of 90 days. After decrease in antibody titre will result in compromised immunity against Covid 19. At this point administration of proposed Ayurvedic capsule will enhance the cellular immunity. Ayurvedic composition having 10 – 12 herbomineral ingredients such as capsule can enhance the production of covid specific antibodies by acting on T cells and B cells which are already producing antibodies against Covid 19 due to administration of Covaxin. Administration of IP 3 capsules can act on T cells and B cells to increase the antibodies against Covid 19. Eventually resulting in prevention of Covid 19 infection.
Traditional medical practitioners use botanicals and other natural substances to stimulate or potentiate the body's own defence mechanisms. This way the body's natural balance is preserved, and side effects are either not present or substantially

reduced. Although both vaccines and botanicals elicit an immune response, vaccines boost the body's response to a specific pathogen whereas botanicals tend to enhance overall immunity. Immune-potentiating botanicals are also used to increase the effectiveness of drugs and reduce side effects.
Keeping population healthy and boosting with immunity is challenging and
presently a lot of research has been undertaken for achieving this goal.
In Ayurveda, Rasayana is a specialized therapy practicised since ages by the ancient
Indian physician to combat the adverse effect of senility and keep the
youngness prolonged. It is the Ayurvedic practice of rejuvenation therapy.
Rasayana is the preventive therapy which is helpful to maintain health, retard aging
process and promote immune system to fight against infection.
The common medicines in Ayurveda with Rasayana properties include
Emblica officinalis, Sida cordifolia, Semicarpus, anacardium, Tinospora cordifolia,
Centella asiatica, Piper longum, Zingiber officinale Convolvulus pluricaulis,
Asparagus racemosus, Anethumsowa, Shilajit, Terminalia chebula , Embelia ribes,
Glycyrrhiza glabra and Withania somnifera.
The present inventors have come up with crucial combination of rasayana herbs
with minerals in specific doses such that a single composition having at least 10
herbomineral ingtredients, preferably 11 – 12 herbomineral ingredients with
reduced doses for each herbomineral ingredient can act synergistically and without
any side effects.
The rasayana herbal medicines are preferably in the form of ‘Ghan’ and minerals
are preferably in the form of ‘Bhasma’ or in ‘Colloidal’ or in ‘Nano particulate’
form.Herbs are preferably in the form of Ghan and Minerals are preferably in the
form of bhasma or in colloidal or in nano particulate form.
Usually, rasayana herbs are administered in high doses such as 500 mg to 2 g in one
or 2 - 4 divided doses. Brahma Rasayana available for sale are usually in the form
of Churna and daily dose is 10 g minimum.

By combining from 5 – 10 rasayana herbs and from 1 – 4 minerals in preferably 1 – 4 and most preferably 2 – 3 compositions, inventors are able to employ much lower doses than recommended to achieve same or even better effects and without any side effects. Thus, it is possible to combine so many rasayana medicines in just 1 – 4 compositions / preparations, preferably, 2-3 compositions / preparations which otherwise are separately administered because of their individual large doses and because it is cumbersome to take 5 – 10 different preparations / compositions.
Since the present composition provide ways to combine 5 – 10 different herbal rasayana medicines with 1- 4 minerals, the synergistic action of all herbal and mineral preparations greatly reduced the total daily intake of each medicine. Ginger when used in solid form i.e. either dry powder / ghan form, the daily dose of 1 g -1.5 g is reduced from 25 – 250 mg, and most preferably, 25 – 150 mg or 25 – 100 mg and even such reduced doses have been found sufficient and produce same or even better action.
Preferably the rasayana herbs selected are those which are reported to have immunomodulatory actions such as Emblica officinalis, Tinospora cordifolia, Piper longum, Zingiber officinale, Asparagus racemosus, Terminalia chebula , Embelia ribes, Glycyrrhiza glabra, Withania somnifera and Convolvulus pluricaulis.
Zingiber officinale
Ginger is a spice consumed worldwide for culinary and medicinal purposes. Ginger plant has a number of chemicals responsible for its medicinal properties, such as antiarthritis, antiinflammatory, antidiabetic, antibacterial, antifungal, anticancer, etc.Ginger contains many volatile oils (sesquiterpenes) and aromatic ketones (gingerols). Gingerols are believed to be the more pharmacologically active constituents of ginger.
Nathorn Chaiyakunapruk et al has concluded that a fixed dose at least 1 g of ginger is more effective than placebo for the prevention of postoperative nausea and vomiting and postoperative vomiting.

Ginger is one of the most effective natural immunomodulator [Radha Singh*, and Kusum Singh, 2019]. An in vitro study found that ginger inhibited lymphocyte proliferation; this was mediated by reductions in IL-2 and IL-10 production [Wilasrusmee C et al, 2002]. Aqueous ginger extract significantly increased the production of IL-1β, IL-6 and TNF-α inactivated peritoneal mouse macrophages and splenocyte proliferation and cytokine production [Ryu HS and Kim HS, 2004]. Ginger rhizome diet for 12 weeks showed increased haematocrit, haemoglobin, erythrocyte, MCH, MCHC, WBC values and neutrophils percentage. Ginger essential oil showed improvement in humoral and cell mediated immune response in immune suppressed mice. [Carrasco FR et al, 2009]. The powdered ginger rhizome is capable to improve non-specific immune response in rainbow trouts [Haghighi M, Rohani MS, 2013].
Thus, Zingiber officinale is selected one of the herbal medicine to prepare compositions of the present invention.
Andrea Gordon, and Abigail Love under chapter 54 of Integrative Medicine (Fourth Edition) 2018, Pages 542-549.e2 provide various doses used by various researchers for Zingiber officinale. These doses are 1000 mg daily in 2 -3 divided doses or a higher dose of 650 mg three times daily. It is further mentioned that the total dose of less than 1500 mg daily is more effective.
2.Embelia ribes-
Embeliaribes comes under rasayana plants. (Rasayana implies to the circulation of
nutrients). Rasayana is a substance that nourishes and tones the entire body.
Gupta et al (Asian Jr. Multidisciplinary Studies, 2015, Vol.3(2))
cites reference of Bhandari U et al (2007) providing that the ethanolic extract of
Embeliaribes enhances the antioxidant defense against reactive oxygen species
produced under hyperglycemic condition and this protects β-cells against loss, and
exhibit antidiabetic property. Embeliaribes extract has shown to enhance
antioxidant defense and neuroprotective activity.
Wang P et al (2020) has reported that their findings indicate that the use of an
adjuvant of embelin, a small molecular inhibitor of XIAP, increased the replication

of oncolytic vaccinia virus (OVV) by mitigating antiviral innate immunity and further indicate utility of embelin as an adjuvant for oncolytic viro-immunotherapy.
3.Terminalia chebula-
This herb is extremely rich in medicinal properties. It is a constituents of the popular
Ayurvedic formula Triphala (which contains equal proportions of Haritaki, Bahera
(Terminalia bellerica) and Amla (Emblica officinalis).
It directly acts on the gastro-intestinal tract and reduces the passage of harmful
toxins to the liver and kidneys.
Terminalia chebula contains several antiaging phenolic compounds are present in
T. chebula. It includes gallic acid, chebulinic acid, isoterchebulin, punicalagin and
1,3,6-tri-O-galloyl-d-glucopyranosehave. These phenolic compounds have
antioxidant activities.
H. N. Shivprasad et al’s study (2006) has shown that Terminalia chebula extract
displays a dose-dependent immunostimulatory effect in relation to antigenic s
Terminalia chebula extract produced a dose-dependent increase in both the
parameters (i.e., antibody production and delayed-type hypersensitivity).
Therefore, they concluded that the aqueous extract of fruit of Terminalia chebula
has promising immunostimulant properties.
Belapurkar, Pranoti et al (2014) reports work of several researchers wherein T.
chebula has been reported to be an effective antibacterial agent against a wide range
of Gram-positive and Gram-negative bacteria, antifungal agent against various
pathogenic fungi and an antiviral agent against swine influenza A virus, HSV-1,
HIV-1 and cytomegalovirus.
Further the same paper reports studies conducted by various researchers
i) that have also inferred that the fruits of T. chebula act strongly against HBS
antigen, inhibit HBV DNA polymerase and also significantly increased IFN-γ and
IL-2 levels in peripheral blood mononuclear cell culture, thus emphasizing its
antiHBVactivity,;
ii) that have indicated it to be used as an antioxidantantiinflammatory,
antianaphylactic, antimutagenic, antinociceptive and in wound healing activities;

iii) that indicated that the biologically active compounds such as chebulagic acid,
gallic acid and ellagic acid make T. chebula highly potent antioxidant, which may
be responsible for its immunomodulatory activity; and
iv) that indicates that its extract neutralizes reactive oxygen species (ROS) and
scavenges free radicals. The free radicals are responsible for causing inflammation
by stimulating release of cytokines such as IL-1, TNF-α and IFN-β, which stimulate
additional neutrophils and macrophages at site of inflammation.
Belapurkar et al (2014) further mentions that different antioxidants of the T.
chebulaextract exhibit immunosuppressive properties, which help in neutralizing
these important inflammatory mediators.
4.Tinospora cordifolia-
Tinosporacordifolia is an important medicinal plant. Through centuries, it has been extensively used in traditional medicinal reparations for treating various ailments. A variety of plant-derived materials polysaccharides, lectins, peptides etc. have been reported to stimulate immune system. Extract of T. cordifoliaposses good immunomodulatory activity.
Aher and Wahi (2010) reported that an oral administration of T. cordifolia alcoholic extract (100 mg/kg, p. o) in male wister rats was found to increase foot pad thickness which indicates immunomodulatory effects of T. cordifolia as compared to vehicle and cyclophosphamide treated groups.
5.Asparagus racemosus-
Asparagus racemosus is an important medicinal plant of tropical and subtropical India. Its medicinal use has been accounted in Indian and British pharmacopoeias and in indigenoussystem of medicine.
The dried roots of the plant are used as drug. The roots are said to be tonic and diuretic and galactgogue, the drug has ulcer healing effect probably via strenthening the mucosal resistance or cytoprotection. It has also been identified as one of the drugs to control the symotoms of AIDS. A. racemosus has also been successfully by some Ayurvedic practitioner for nervous disorder, inflammation and certain infectious disease (Shashi Alok et al, 2013)

Sharma M. et al (2016) cites paper by Gautam et al (2009) mentioning that
Asparagus racemosus extract has shown immunoadjuvant potential and another
paper by Goyal, Singh et al (2003) mentioning oral administration of decoction of
powdered root of A. racemosus has been reported to produce leucocytosis and
predominant neutrophilia along with enhanced phagocytic activity of the
macrophages and polymorphs.
Pooja Shaha and Anurag Bellankimath report as follows:
i) Racemosus root extract modulated action of immune system;
ii) It induces the immune system to fight against immune deficiencies and
infections;
iii) It might be helpful in obtaining higher protective antibody against different
vaccinations including more effective cell mediated immune response for
protection against various bacterial, viral and other diseases.
Akansha Singh & B. Sinha (2014) report that Several workers have studied the
effect of A. racemosus root extract in augmentation of humoral and cell mediated
immune responses providing better protection level against infections.
6.Emblica officinalis-
Emblica officinalis enjoys a hallowed position in Ayurveda-an Indian indigenous system of Medicine. According to believe in ancient Indian mythology, it is the 1st tree to be created in the universe (Grover, Herpreet Singh et al, 2020). Fruit and its extract is widely used as phytomedicines. It is one of the richest source of natural vitamin C and low molecular weight hydrolysable tannins. This makes it a good source of antioxidant. It has antimicrobial activities which includes antibacterial, antifungal and antiviral properties.
Charmkar N.K and Singh, Rajesh report beneficial role of Emblica officinalis in cancer, diabetes, liver treatment, heart trouble, ulcer, anemia and various other diseases and particularly its application as antioxidant, immunomodulatory, antipyretic, analgesic, cytoprotective, antitussive and gastroprotective. Further they particularly report role of Emblica officinalis to modulate the immune system and the inflammatory response.

Suja RS et al evaluated aqueous extract of dried Emblica officinalis Gaertn. (Amla) fruit pulp powder for immunomodulatory effect on male Swiss Albino mice. The mice were divided into three groups. The first group received vehicle alone to serve as control. The second and third groups received the extract orally at 100 and 200 mg/kg body weight dose levels respectively per day for a period of 19 days. Suja RS et al further reports that there was significant dose dependent increase in haemagglutination antibody titre, sheep red blood cells induced delayed type of hypersensitivity reaction, macrophage migration index, respiratory burst activity of the peritoneal macrophages, total leukocyte count, percentage lymphocyte distribution, serum globulin and relative lymphoid organ weight in Emblica treated mice indicating its ability to stimulate humoral as well as cell mediated immunity.
7.Withania somnifera-
Ziauddin, M et al report that W. somnifera prevented myelosuppression in mice treated with immunosuppressive drugs . It was observed in Ashwagandha-treated mice as compared with untreated (control) mice. We also report an immunostimulatory activity treatment with W. somnifera was accompanied by significant increases in hemolytic antibody responses towards human erythrocytes. L. Davis et al (2002) mention that the role of W. somnifera as immunomodulator has been extensively studied. In a mouse study, WS root extract enhanced total white blood cell count. In addition, this extract inhibited delayed-type hypersensitivity reactions and enhanced phagocytic activity of macrophages when compared to a control group.
L. Davis and G. Kuttan, (2000) report that administration of W. somnifera also showed an enhancement in phagocytic activity of peritoneal macrophages when compared to control in mice. These results confirm the immunomodulatory activity of W. somnifera extract in indigenous medicine.
8.Piper longum -
Chauhan Khushbu et al (2011) report that tests such as haemagglutination titre (HA), macrophage migration index (MMI) and phagocytic index (PI) have

demonstrated the immunostimulatory action of P.longum to be both specific and non specific.
Piper longum is well known for its medicinal and pharmaceutical importance. Tripathi D. M et al report that the specific and nonspecific immune-stimulatory actions of P. longum fruits have been evaluated by hemagglutination titer, macrophage migration index, and phagocytic index. It is found to activate macrophages, as shown by an increased macrophage migration index and phagocytic index, indicating immune-stimulatory activity.
9. Glycyrrhizra glabra-
The name glycyrrhiza is derived from Greek words meaning "sweet roots”.
• Therapeutic use of licoricedates back to the Roman Empire. The Greek physician Hippocrates (460 BC) and botanist Theophratus (371 BC) extolled its uses.
• Licorice root contains a variety of compounds, including triterpenoids, polyphenols, and polysaccharides (starches, mannose, and sucrose). Polyphenols include certain phenolic acids, such as liquiritin, flavones and flavans; chalcones; and isoflavonoids, such as glabridin.
• The activity of licorice on the immune system has been described as "nonspecific" by most investigators. This means licorice stimulates, activates or promotes an immune response in multiple ways.
S. Rao Chavali et al report on Glycyrrhizic acid that the experimental data suggest that different components in the Quillaja saponin preparations may have selective effects on various subtypes of cell populations. Glycyrrhizic acid has the most profound immunomodulatory activity in vitro. Activation, proliferation and differentiation steps of lymphocytes appear to be mediated by secretion of soluble factors.
Minerals

The present invention combines above mentioned rasayana herbal medicines preferably around 5 – 10 rasayana herbs in the form of powders / Ghan with 1 - 4 minerals preferably in the form of bhasma or in colloidal or in nano particulate form in such a way that they can be combined in two or more preparations and administered together, simultaneously or sequentially to impart / boost immunity to humans and mammals thus building ability to identify and resist large numbers of infectious and potentially harmful microorganisms, enabling the body to prevent or resist diseases and inhibit organ and tissue damage. The preparations so combined and administered can help patients.
10. Calcium
A study conducted by Razzell et al (2013) in the University of Bristol on cellular processes underlying the body's response to healing has shown for the first time how a flash of calcium is the very first step in repairing damaged tissue. The findings could lead to new therapies that speed up the healing process following injury or surgery.
11.Calcined Zinc –
Due to antioxidant effects of Zinc it protects against ROS and RNS. Zinc helps modulate cytokine release and induces proliferation of T cells and helps to maintain skin and mucosal membrane integrity.
Silvia Maggini et al referring previously conducted research report that Zinc has a central role in cellular growth and differentiation of immune cells. It is essential for intracellular binding of tyrosine kinase to T cell receptors, required for T lymphocyte development and activation. Zinc supports Th1 response.
Melinda A. Beck reports that Zn is perhaps one of the most studied trace elements with respect to its effect on the host immune system and that Zinc deficiency has been noted to result in increased susceptibility to infectious disease. Suboptimal Zinc status has also been associated with decreased T-cell function and antibody responses. If the Zinc deficiency is corrected, immune status is restored . Zinc is an

essential cofactor for thymulin, a peptide hormone that plays a key role in T-cell
maturation.
Additionally, minerals Silver and / or gold can be added in bhasma or in colloidal
or in nano particulate form.
The herbomineral composition of the invention shall be administered 1 – 2 dosage
forms once or twice a day for a period from a week to up to a month or longer
based on requirement.
Example 1
Formulations of present invention are as follows:

Heromineral Comp Comp Comp For one For two
ingredients 1 2 3 dosage form dosage forms
Preferred composition given
for clinical tria l
Withania P P P 50 - 75 mg 100 -150
somnifera
Terminalia P P P 50 - 75 mg 100 -150
chebula
Tinospora P P P 37.5 – 62.5 mg 75 - 125
cordifolia
Emblica P P P 30 – 60 mg 60 - 120
officinalis
Asparagus P P P 20 – 40 mg 40 – 80 mg
racemosus
Piper longum P A P 0.025 - 10 mg 0.05 – 20.0
Zingiber P P A 30 – 50 mg 60 – 100
officinale
Embelia ribes P P P 50 – 62.5 mg 100 – 125
Glycyrrhiza P P P 30 – 50 mg 60 - 100
glabra

Jasad Bhasma P P P 10 – 30 mg 20 – 60
Shankh A P P 50 - 75 mg 100 - 125
Bhasma
powder
Excipients
optional
Result and Conclusion from clinical study:
The four immunological markers IgG spike, CD3+, CD4+ and CD8+ were evaluated on subjects in both test and control groups at visit 1 and visit 4. At visit 1, the mean (geometric) concentration of IgG was higher in test group as compared to placebo group. The other parameters were similar and insignificantly different between two groups. At visit 4, for IgG, the difference of means between two groups was statistically significant. There was a significant reduction in the IgG levels in placebo group, while in test group, the mean concentration was almost retained. The other markers remained un-altered in both the groups at visit 4. In earlier study by Saleh MM (2020), the values of CD3+ and CD4+ were found lower in COVID-19 infected patients as compared to normal individuals, while that of CD8+ were higher in such patients. In the present study, the mean values for CD3+, CD4+ and CD8+ were close to normal individuals, at both visit 1 and visit 4. When the % values of these parameters were compared between two groups at visit 4, CD3+ was within the reference range in 93.3% subjects from test group, as compared to 86.7% in placebo group (p=0.999). CD4+ was within reference range in all 100% of subjects in both the groups, while CD8+ was within reference range in 100% of subjects from test group and 80% of subjects from placebo group (p=0.224). For CD8+, the difference was insignificant due to small sample; however, was in favour of the test group. Also the finding on IgG was also in favour of the test group.
Example 2: Process of Preparation 1. Rasayana Herbs

Herbal medicines are preferably provided in ghana form. The process of preparing Ghan form can be from water / aqueous extract or from super critical extraction process. Any other extraction process used for preparing ghan can also be adopted. The processes are provided under Figures 1 - 3.
The administration is by oral route and accordingly oral solid and liquid compositions are designed.
2. Bhasma preparation
Minerals calcium and zinc can be converted into Bhasma form by usual reported processes. Alternatively, shankh bhasm and Jasad bhasm can be incorporated. Preferably, the particle size of calcium and zinc in bhasma are such that 90 % particles are below 50 µM, more preferably below 15 µM and most preferably below 1 µM. Alternatively, colloidal or nano particulate forms are used. The particle size of mineral in these forms is found to be crucial.
Zinc content can vary in bhasma form. In an embodiment, zinc content is around 70 %. Calcium content in an embodiment of bhasma is around 40 %.
3. Preparation of compositions:
The ghan of different rasayana herbs are mixed and blended further with one or more mineral in form of bhasma (or alternative forms). Suitable pharmaceutically acceptable excipients / adjuvants are added and blended further. Excipients include one or more of diluents, binders, glidants, lubricants and disintegrants. A process to prepare herbomineral composition comprises
i) preparing Ghan form of one or more rasayana herbs from water /
aqueous extract or from super critical extraction process;
ii) preparing Bhasma preparation of calcium and / or zinc wherein 90
% particles are below 50 µM, more preferably below 15 µM and most preferably below 1 µM. or Alternatively, preparing colloidal or nano particulate forms; and

iii) optionally mixing / blending ghan form and Bhasma form to prepare
herbomineral composition.
The words preparation and compositions are used synonymously.
The composition can be selected from tablet, capsule, caplets, coated tablets, multi-layered tablets, minitablets, pill, powder, granules, seeds, pellet, extrudates, spheronized material, compacts, particulate preparation, dispersion, dispersible tablet, fast disintegrating tablet, lozenge, sublingual or buccal tablets, powder mixture, syrup, suspension, powder for oral solution, powder for oral suspension injectables, liquid, solution, subcutaneous, intravenous, intramuscular composition. In an embodiment, the composition is a capsule. In another embodiment, the composition is tablet. In one more embodiment, the composition is syrup or suspension. In yet another embodiment, the composition is powder, powder for oral suspension, powder for oral solution or granules.
Multi-layered tablets, coated tablets and modified release compositions are also
prepared where release is modified to suit sustained release, extended release,
delayed release of herbal medicines and minerals. Alternatively, one or few herbal
medicine or mineral can be in modified release form and other herbal medicines
and minerals are in immediate release form.
Generally, excipients occupy from 2 – 40 % preferably from 5 – 30 % of the final
compositions.
The compositions of the present invention preferably include tablet, dragee, capsule, caplet, orally-disintegrating tablet, film-coated tablet, enteric tablet, buccal tablet, sublingual tablet, chewable tablet, effervescent tablet, slow-release tablet, rapid-release tablet, modified-release tablet, delayed-release tablet, prolonged-release tablet, controlled-release tablet, sachet, granule, pilule, powder, pellet, , pastille and similar solid oral dosage forms.
Other excipients are chosen based on the composition to facilitate the physical formulation of various dosage forms. Pharmaceutical composition of the present inventions may comprise along with the active and a solubilizer, other

pharmaceutically acceptable excipients like diluents / fillers, disintegrants, binders, lubricants, glidants, and the mixtures thereof, to facilitate the physical formulation of various dosage forms.
Binders can be selected from the group, but are not limited to methylcellulose, sodium carboxymethylcellulose, calcium carboxymethylcellulose, ethyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, silicified microcrystalline cellulose(SMCC), polyvinyl pyrrolidone, gelatine, polyvinyl alcohol, acacia, tragacanth, guar, pectin, starch paste, pregelatinized starch, alginic acid, compressible sugar, liquid glucose, dextrates, dextrin, dextrose, maltodextrin, guar gum, magnesium aluminium silicate, polymethacrylates, sorbitol and other materials known to one of ordinary skill in the art. A mixture of binders may also be used. The binder is preferably used in an amount of from about 2 to about 15% by weight.
Disintegrant can be selected from the group, but are not limited to a!ginic acid,
carboxymethylcellulose calcium, carboxymethyl cellulose,
carboxymethylcellulose sodium, cross-linked sodium carboxymethylcellulose, low substituted hydroxypropyl cellulose, colloidal silicon dioxide, croscarmellose sodium (CCS), crospovidone, guar gum, magnesium aluminium silicate, microcrystalline cellulose (MCC), methyl cellulose, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidones, polacrifin potassium, starch, pregelatinized starch, sodium alginate, sodium lauryl sulphate, sodium starch glycolate, crystalline cellulose, hydroxypropyl starch and other materials known to one of ordinary skill in the art. The combination of above-mentioned disintegrants can also be used.
Preferably, the disintegrant is selected from the group consisting of croscarmellose sodium, crospovidone and sodium starch glycolate. Disintegrant is preferably used in an amount of from about 1% to about 20% by weight of the tablet, more preferably in an amount of from about 2% to about 15% by weight and most preferably in an amount of from about 2% to about 10%.

In an embodiment, disintegrant is 3.2 % of the core tablet weight. In another embodiment, disintegrant is 4.6 % of the core tablet weight. In few embodiments, the disintegrant is from 5.5 to 5.7 % by weight of the tablet.
Diluents or filler can be selected from the group consisting of calcium carbonate, calcium phosphate, calcium sulphate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, fructose, lactose, maize starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, maltitol, microcrystalline cellulose, powdered cellulose, pregelatinized starch, sorbitol, starch, sucrose, sugar spheres, talc, tribasic calcium phosphate, and xylitol and other materials known to one of ordinary skill in the art.
Preferred diluents or fillers include lactose, fructose, starch, sucrose, mannitol, maltitol, sorbitol, xylitol and microcrystalline cellulose.
Binder can be selected from the group, but is not limited to methylcellulose, sodium carboxymethylcellulose, calcium carboxymethylcellulose, ethyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, silicified microcrystalline cellulose(SMCC), polyvinyl pyrrolidone, gelatine, polyvinyl alcohol, acacia, tragacanth, guar, pectin, starch paste, pregelatinized starch, alginic acid, compressible sugar, liquid glucose, dextrates, dextrin, dextrose, maltodextrin, guar gum, magnesium aluminium silicate, polymethacrylates, sorbitol and other materials known to one of ordinary skill in the art. A mixture of binders may also be used. The binder is preferably used in an amount of from about 1 to about 15% by weight, preferably from about 1 – 10 % by weight of the tablet.
Lubricants can be selected from the group consisting of vegetable oils, such as hydrogenated vegetable oil or hydrogenated castor oil; polyethylene glycols, such as polyethylene glycol (PEG)-4000 and PEG-6000; stearic acid; derivatives of stearic acid, such as magnesium stearate, sodium stearate, calcium stearate, zinc stearate, glyceryl monostearate, glyceryl palmitostearate and sodium stearyl fumarate; mineral salts, such as talc; inorganic salts; organic salts, such as sodium

benzoate, sodium acetate, sodium chloride and sodium oleate; and polyvinyl alcohols, microcrystalline cellulose, sodium lauryl sulphate, silica, colloidal silica, corn-starch, calcium silicate, magnesium silicate, silicon hydrogel and other materials known to one of ordinary skill in the art.
The preferred lubricant is magnesium stearate. Preferably, lubricant is used in an amount from about 1 to about 5% by weight.
Glidants can be selected from the group, but is not limited to colloidal silicon dioxide, colloidal silica, corn-starch, talc, calcium silicate, magnesium silicate, magnesium trisilicate, amorphous silica, colloidal silicon, silicon hydrogel, powdered cellulose, silicon dioxide, talc, and other materials known to one of ordinary skill in the art.
Preferably, talc is used as a glidant. More preferably, colloidal silicon dioxide is used as a glidant. Most preferably, combination of talc and colloidal silicon dioxide is used as a glidant.
Glidants are used in an amount from about 0.5 to about 10 % by weight of the core tablet. Preferably, from about 1 to about 5 percent by weight of the tablet. One of the preferred solid dosage form is a capsule dosage form. It can contain a mixture of herbal powders and minerals in the form of bhasma or in colloidal or in nano particulate form and necessary adjuvants.

Alternatively or additionally, additives, adjuvants , excipients provided in table xyz
are added.
Table A: additives, adjuvants , excipients according to Ayurveda
List of Additives permitted in Ayurveda Aahara

No. Food Additive. Mnximant permitted Level V jactuinaL CIBQEI
1. Guar Arabic Acacia pun (INS4I4) 2% Thickener. stabilizer
2 Tragacanth gum 2%

_3 Guar gum (INS 412) 2%

4. Pectins (INS 440) GMP*

5 Gum karaya (INS 416) GMP*

6. Konjac flour (INS 425) GMP*

7. Starch and starch derivatives permitted in FSSR GMP*

8 Hoaey GMP* Sweetening agent
9. Jaggery GMP*

10. Date Syrup GMP*

11. Mollasses 5%

12 Curcumin (IN5 100) (i) GMP* Co lour
13 Turmeric (INS 100(ii) GMP*

14. Paprika Paprika Exliacc Pjpciki Oleoresin (INS 160 (ii)) GMP*

15. Annatto extract,. norbixin -based)(INS 160b (ii)) 100mg/kg

16. Annatto extract,. norbixin -based)(INS 160b (ii) 50mg/kg

17. Chlorophyll A and Chlorophyll B(INS 140) 100mg/kg

18, Anthacyanins (INS163) GMP*

19. Caramel plain (]?Oal GMP*

20. Concentrated water extract of a colored Fruit or vegetable listed under FSSR (Colouring foods) GMP*

21. Aortic acid f INS 2)60) GMP*
Acidity regulator
22. DL-Lactk acid (IN5 270) GMP*

23 Citric acid (INS 330) GMP*

24. Tartaric acid (INS 334) GMP*

25. DL-Malic acid (INS 296) GMP*
26. L-Ascorbic acid (INS 300) GMP*

27. Rose oil 1% Flavouring agent
28. Kewda/Kewra (oil from Ketaki) 0.5%
29. Rosemary oil 1% Antioxidant
30. Distilled oils of spices 2% Preservatives, flavouring agent
31. Powders of spices 1% Flavouring agent, colouring agent
32. Nibu satva (citric acid) GMP* Acidity regulator, flavour enhancer
* Quantity of the additive added to food shall be limited to the lowest possible level necessary to accomplish its desired effect.
The other dosage form is a tablet containing a mixture of herbal powders and minerals in the form of bhasma or in colloidal or in nano particulate form and necessary adjuvants.
Yet one more dosage form is a taste masked syrup or suspension containing dissolved / partially dissolved or finely suspended mixture of herbal powders and minerals in the form of bhasma or in colloidal or in nano particulate form and necessary adjuvants.
Herbs are preferably in the form of Ghan and Minerals are preferably in the form of bhasma or in colloidal or in nano particulate form. Any suitable method can be used to prepare Ghan. Alternatively, minerals can be in their oxides, hydrates, solvates and salt forms. For example, if calcium is chosen as a mineral, it can be provided in inorganic or organic form such as calcium chloride, calcium carbonate, calcium phosphate, tricalcium citrate, calcium lactate, calcium lactate gluconate, calcium gluconate and calcium orotate.
Preferred zinc form is calcinated zinc, zinc oxide or salts with acetate, gluconate, and sulfate.
The advantages of the invention is as follows.
Usually, rasayana herbs are administered in high doses such as 500 mg to 2 g in one or 2 - 4 divided doses. Brahma Rasayana available for sale are usually in the form of Churna and daily dose is 10 g minimum. By combining from 10 - 12 hrbomineral

ingredients in reduced dosage, inventors are able to employ much lower doses than recommended to achieve same or even better effects and without any side effects.
Thus, it is possible to combine many rasayana medicines in just single composition.
Since the present composition provide ways to combine 10 – 12 herbomineral ingredients, the synergistic action of all herbal and mineral preparations greatly reduced the total daily intake of each medicine. For example, Ginger when used in solid form i.e. either dry powder / ghan form, the daily dose of 1 g - 1.5 g is reduced from 25 – 250 mg, and most preferably, 25 – 150 mg or 25 – 100 mg and even such reduced doses have been found sufficient and produce same or even better action.
Reduced dosage means dose is reduced to 1 – 50 % of the usual dose of herbal medicine or mineral. Preferably, dose is reduced to 1 – 25 % of the usual dose of herbal medicine or mineral.
Analysis of herbomineral compositions
The rasayana herbs / herbomineral compositions will be subjected to following analytical processes to estimate active contents or marker compounds from rasayana herbs / compositions.

1 2 3 4 5 6 7 8 9 Product Standardization parameter

Ginger Gingerols Content by HPLC

Vavding Embelin by HPLC

Licorice Glycyrrhizin content by Gravimertric

Haritaki Chebulinic acid, Chebuloside II by HPLC

Guduchi Cordiofolioside A by HPLC

Shatavari Shatawarin IV Content by HPLC

Amla Gallic and Ellagic Acid By HPLC

Ashwagandha Withanolides by Gravimetric

Long pepper Piperine Content by HPLC

Clinical Study Details STUDY OBJECTIVE
Primary Objective
The primary study objective is to evaluate the immunogenicity enhancement (specific cellular immune responses (CD3+, CD4+, and CD8+) of an herbal formulation in patients vaccinated with 2 doses for COVID-19.
Secondary Objective
The secondary study objective is to evaluate changes in COVID-19 antibodies (IgG antibody for RBD and Spike protein) in patients who received herbal formulation (post receipt of 2 doses of vaccination).
STUDY DESIGN, MATERIALS AND METHODS
Study Design
The study was designed as a Randomized, Double-blind, Placebo Controlled, Parallel-Group, Proof of Concept study to Assess the Safety and Immunogenicity of ,IP 3 Capsules in Indian Healthy Subjects who have completed the vaccination (COVAXIN) for COVID-19.
Methodology
COVID-19 vaccinated volunteers will be enrolled into the study after obtaining Ethics Committee approved Informed Consent, in writing from the subjects. In Part A, all 30 subjects will receive either active or placebo, for twenty-eight (28) consecutive days.
• On Screening (Day -3): Investigator will identify the subjects to evaluate
eligibility of the patients. Signed ICF will be obtained from the subject before

initiating any study related activity. Once ICF is signed by subject and PI, Subject’s demographics (age, gender, height, weight), vital signs (pulse, temperature, blood pressure, heart rate), physical examination, medical history and medication history shall be recorded. Urine pregnancy test shall be performed for female subjects of childbearing age. Blood samples shall be collected for lab investigations. Nasopharyngeal swab sample will be collected to perform RT-PCR test. Copies of authentic records of completion of 2 vaccine doses of COVAXININ shall be obtained from the subjects and shall be verified. Subjects shall be evaluated again at baseline (Day 0) for their eligibility criteria to participate in the study, post receipt of the lab reports.
• Baseline Visit (Day 0): Patients will visit the site for baseline activities on day 0. After all the lab reports are received, evaluate the patient for eligibility as per ICEC. Only those subjects who meet all the inclusion criteria and none of the exclusion criteria shall be enrolled during this visit. Vital signs (temperature, blood pressure, pulse & heart rate), physical examination shall be recorded. Investigational Products (either active or placebo) shall be dispensed as per the randomization code list generated by an independent statistician. Adverse and serious adverse events if any will be recorded. Concomitant medications shall be recorded.
• Day 14±2days: Subjects will bring unused IP bottles on this study visit. Vitals and physical examination, will be recorded. Investigational Products sufficient until the next visit will be dispensed. Adverse and serious adverse events if any will be recorded. Concomitant medications shall be recorded. Compliance to the Investigational product shall be recorded. Investigational product shall be recorded.
• End of Study Treatment (Day 28±2days): Subjects will bring unused IP bottles on this study visit. Vitals and physical examination, will be measured. Blood samples shall be collected for lab investigations and safety assessments. Urine

pregnancy test for female patients of child bearing potential shall be performed once again during this visit. Adverse and serious adverse events if any will be recorded. Concomitant medications shall be recorded. Compliance to the Investigational product shall be recorded.
• Telephonic Follow Up (within 14 days): Subjects will be contacted
telephonically within 14 days from the last dose taken by the subject, to record over
all wellbeing of the subjects and AE and SAE experienced, if any.
Rationale for Study Design
Proposed IP 3 capsule contains ingredients with medicinal properties like antiviral, anti-inflammatory, analgesic, immunomodulatory, antioxidant etc. Synergic effect of these ingredients will act as immunomodulator in subjects who have received 2 doses of Covaxin. After receiving Covaxin to generate immunogenicity against Covid 19, subject will have 100 % antibodies against the Covid 19 for period of 90 days. After decrease in antibody titre will result in compromised immunity against Covid 19. At this point administration of proposed Ayurvedic capsule will enhance the cellular immunity. Ayurvedic capsule will enhance the production of covid specific antibodies by acting on T cells and B cells which are already producing antibodies against Covid 19 due to administration of Covaxin. Administration of Abayakastha Plus capsules will act on T cells and B cells to increase the antibodies against Covid 19. Eventually resulting in prevention of Covid 19 infection.
Number of Patients
The study was planned to recruit 30 patients from 01 sites.
Selection of Patients
Inclusion Criteria
Subject met all of the following criteria were included in the study.
• Written informed consent of a subject to participate in the trial
• Males and females aged 18+ years and 70 years.

Treatment of patients
This was a Randomized, Double-blind, Placebo Controlled, Parallel-Group, Proof of Concept study to Assess the Safety and Immunogenicity of ,IP 3 Capsules in Indian Healthy Subjects who have completed the vaccination (COVAXIN) for COVID-19.
Treatment of patients
This was a Randomized, Double-blind, Placebo Controlled, Parallel-Group, Proof of Concept study to Assess the Safety and Immunogenicity of ,IP 3 Capsules in Indian Healthy Subjects who have completed the vaccination (COVAXIN) for COVID-19.
Description of Study Drug

Study Drugs Investigational Product
Product Name Investigational Product 3
Dosage Form Capsule
Dosage 450 mg twice a day after meal
Route of Administration Oral
Treatment Compliance
The administration of study drug was recorded in the appropriate sections of the eCRF. Patients were asked to return all unused investigational product to the

hospital at each visit. Compliance was assessed based on returned tablet counts
recorded in the CRF.
To be considered compliant in terms of IP administration, patients needed to
consume ≥ 80% of the doses of medication as specified above in the treatment
compliance.
Patients who do not complete the ≥ 80% dosing schedule within the specified time
window were considered as non-compliant.
Concomitant Medications
Enrolled patients were on only IP during the study period.
ASSESSMENT OF EFFICACY
As per Sponsor recommendation 30 A Randomized, Double-blind, Placebo Controlled, Parallel-Group, Proof of Concept study to Assess the Safety and Immunogenicity of ,IP 3 Capsules in Indian Healthy Subjects who have completed the vaccination (COVAXIN) for COVID-19.

IP 3 Placebo Overall
Total Number of patients Randomized 15 15 30
Patients in Safety Population 15 15 30
Patients in efficacy population 15 15 30
Lost to follow up 00 00 00
Withdrawal due to disease Progression 00 00 00
Withdraw Consent 00 00 00
AEs 00 00 00

ASSESSMENT OF SAFETY
None of the patients experienced any adverse or serious adverse events during the study period.
Statistical methods Sample size
IP 3 Capsule:
450 mg active investigational product (,IP 3 Capsule) contains herbal extracts of below ingredients:
Formulation of IP 3 is as follows:

For one dosage form For two dosage forms
Withania somnifera 50 - 75 mg 100 -150
Terminalia chebula 50 - 75 mg 100 -150
Tinospora cordifolia 37.5 – 62.5 mg 75 - 125
Emblica officinalis 30 – 60 mg 60 - 120
Asparagus racemosus 20 – 40 mg 40 – 80 mg
Piper longum 0.025 - 10 mg 0.05 – 20.0
Zingiber officinale 30 – 50 mg 60 – 100
Embelia ribes 50 – 62.5 mg 100 – 125
Glycyrrhiza glabra 30 – 50 mg 60 - 100
Jasad Bhasma 10 – 30 mg 20 – 60
Shankh Bhasma powder 50 - 75 mg 100 - 125
Total 357.5 – 602.5
B. Each Placebo Capsule contains Edible starch ~ 450 mg.

Analysis populations STATISTICAL ANALYSIS
The characteristics of patients included in the study were summarized according to scale of measurement. The continuous characteristics (parameters) were expressed in terms of mean, Pearson chi-Square Test while categorical parameters were summarized in terms of numbers and percentages. The comparison of Laboratory test and vital parameters of patients between two time points, namely Day 1 and Day 28, was carried out using paired t-test.
Demographic data
Table 1: Descriptive statistics for characteristics of patients in two study
groups

Treatment arm P-value
Test Placebo

Age in years N 15.00 15.00 0.542*

Mean 35.53 33.07

Standard Deviation 10.97 10.91

Minimum 22 21

Maximum 62 63

Sex Female n 5 4 0.690†

% 33.3% 26.7%

Male n 10 11

% 66.7% 73.3%

Height (cm) N 15.00 15.00 0.675*

Mean 166 165

Standard Deviation 7.69 6.96

Minimum 152 155

Maximum 179 178

Weight (kg) N 15.00 15.00 0.542*

Mean 62 59

Standard Deviation 11.18 8.11

Minimum 40 48

Maximum 85 75

BMI (kg/m2) N 15.00 15.00 0.721*

Mean 22.36 21.92

Standard Deviation 3.76 2.76

Minimum 17.31 17.51

Maximum 34.48 30.04

*Obtained using t-test for independent samples; † Obtained using Pearson’s chi-square test
Table 1 provides the descriptive statistics for demographic and anthropometric characteristics of subjects in two groups. The mean age of patients in test group (35.53 ± 10.97 years) differed insignificantly than that of patients in placebo group (33.07 ± 10.91 years), as indicated by a p-value of 0.542. Further, the sex wise distribution in two groups was statistically insignificant (p=0.690) with male preponderance in each group. The anthropometric parameters viz, height, weight and BMI differed insignificantly between two groups with corresponding p-values 0.675, 0.542 and 0.721 respectively.
Table 2: Descriptive statistics for vital parameters of subjects in two groups at VISIT 1

Treatment arm P-value

Test Placebo
Pulse rate N 15 15 0.268*

Mean 77.53 74.53

Standard Deviation 8.53 5.73

Minimum 64 68

Maximum 90 84

Respiratory N 15 15 0.999*

Mean 18.60 18.60

Standard Deviation .83 .63

Minimum 18 18

Maximum 20 20

Temperature (oC) N 15 15 0.804*

Mean 36.53 36.49

Standard Deviation .44 .57

Minimum 35.60 35.60

Maximum 37.20 37.20

Systolic BP (mmHg) N 15 15 0.344*

Mean 116.67 118.67

Standard Deviation 4.88 6.40

Minimum 110 110

Maximum 120 130

Diastolic BP (mmHg) N 15 15 0.514*

Mean 76.00 77.33

Standard Deviation 5.07 5.94

Minimum 70 70

Maximum 80 90

*Obtained using t-test for independent samples
Table 2 provides the descriptive statistics for vital parameters of subjects in two groups at visit 1. It is evident from the table that all the parameters showed statistically insignificant difference of means between the two arms (p > 0.05).

Table 3: Distribution of subjects in two groups according to physical examination status at VISIT 1

Treatment arm

Test ( n
15
15 15 15 15 15 15 15 15 15 15 15 15 15 15 N=15) Placebo (N=15)

% n %
General appearance Normal
100.0% 15 100.0%
Skin Normal
100.0% 15 100.0%
Ear nose throat Normal
100.0% 15 100.0%
Head neck thyroid Normal
100.0% 15 100.0%
Heart Normal
100.0% 15 100.0%
Lung Normal
100.0% 15 100.0%
Chest Normal
100.0% 15 100.0%
Abdomen Normal
100.0% 15 100.0%
Extremities Normal
100.0% 15 100.0%
Genitelia Normal
100.0% 15 100.0%
Anorectal Normal
100.0% 15 100.0%
Lymph nodes Normal
100.0% 15 100.0%
Musculo-Skeletal Normal
100.0% 15 100.0%
Neurological Normal
100.0% 15 100.0%
Medical history No
100.0% 15 100.0%
Table 3 provides the description of physical examination status of patients at visit 1 in two study groups. All the 15 patients, in either group, had normal presentation on various physical examination parameters as shown in the table. None of the patients from either group had any medical history.
Table 4: Descriptive statistics for haematological parameters of subjects in two groups at VISIT 1

Haematological parameters Treatment arm P-value*

Test Placebo

RBC (million/mm3) N 15 15 0.256

Mean 4.76 4.47

Standard Deviation .79 .53

Minimum 3.62 3.57

Maximum 5.95 5.18

Haemoglobin (gm/dl) N 15 15 0.680

Mean 13.57 13.29

Standard Deviation 1.93 1.80

Minimum 9.08 10.24

Maximum 17.23 16.56

MCV (fl) N 15 15 0.506

Mean 88.57 91.35

Standard Deviation 9.31 12.98

Minimum 75.20 65.60

Maximum 103.10 116.00

MCH (pg) N 15 15 0.442

Mean 28.83 29.99

Standard Deviation 3.62 4.46

Minimum 23.30 20.40

Maximum 33.90 38.10

Haematocrit N 15 15 0.514

Mean 41.77 40.47

Standard Deviation 5.86 4.94

Minimum 29.30 32.90

Maximum 51.90 50.70

Neutrophils (%) N 15 15 0.423

Mean 57.00 54.20

Standard Deviation 9.43 9.43

Minimum 37.00 33.00

Maximum 70.00 72.00

Lymphocytes (%) N 15 15 0.287

Mean 31.20 34.27

Standard Deviation 7.52 7.95

Minimum 21.00 20.00

Maximum 47.00 46.00

Monocytes (%) N 15 15 0.765

Mean 7.80 7.60

Standard Deviation 2.11 1.45

Minimum 4.00 4.00

Maximum 11.00 11.00

Eosinophils (%) N 15 15 0.955

Mean 3.93 3.87

Standard Deviation 3.13 3.31

Minimum 1.00 1.00

Maximum 11.00 14.00

Basophils (%) N 15 15 0.961

Mean .07 .07

Standard Deviation .27 .26

Minimum .00 .00

Maximum 1.00 1.00

WBC (cells/mm3) N 15 15 0.787

Mean 6630.67 6863.33

Standard Deviation 1656.84 2860.66

Minimum 3470.00 3440.00

Maximum 8630.00 16150.00

Platelet N (10^3/ul) N 15 15 0.711

Mean 303.27 293.47

Standard Deviation 52.42 86.89

Minimum 200.00 58.00

Maximum 399.00 432.00

Random
glucose
(mg/dl) N 15 15 0.377

Mean 93.53 99.27

Standard Deviation 14.79 19.79

Minimum 82.00 79.00

Maximum 138.00 154.00

*Obtained using t-test for independent samples
Table 4 provides the descriptive statistics for haematological parameters of subjects in two groups at visit 1. It is evident from the table that all the parameters showed statistically insignificant difference of means between the two arms (p > 0.05).
Table 5: Descriptive statistics for biochemical parameters in two groups at VISIT 1

Biochemical parameter Treatment arm P-value*

Test Placebo

ALT (U/L) N 15 15 0.928

Mean 20.80 20.40

Standard Deviation 12.70 11.41

Minimum 7.00 7.00

Maximum 52.00 52.00

AST (U/L) N 15 15 0.228

Mean 20.80 23.80

Standard Deviation 5.56 7.62

Minimum 13.00 14.00

Maximum 31.00 41.00
Serum creatinine (mg/dl) N 15 15 0.702

Mean .84 .81

Standard Deviation .21 .18

Minimum .54 .53

Maximum 1.20 1.08

Bilirubin (mg/dl) N 15 15 0.148

Mean .53 .41

Standard Deviation .28 .11

Minimum .17 .17

Maximum 1.29 .66

*Obtained using t-test for independent samples
Table 5 provides the descriptive statistics for biochemical parameters of subjects in
two groups at visit 1. It is evident from the table that all the parameters showed
statistically insignificant difference of means between the two arms (p > 0.05).
Table 6: Descriptive statistics for immunological markers in two groups at VISIT
1

Treatment arm P-value*
Test Placebo

IgG spike (BAU/ml) N 15 15 0.619

Geometric mean 546.59 373.31

Geometric SD 6.84 9.17

Minimum 20.99 0.40

Maximum 5140.44 2999.16

CD3+ (%) N 15 15 0.457

Mean 67.98 69.91

Standard Deviation 4.77 8.67

Minimum 59.73 54.23

Maximum 77.38 84.97

38

CD4+ (%) N 15 15 0.743

Mean 37.72 38.47

Standard Deviation 7.23 5.00

Minimum 26.76 29.30

Maximum 52.10 51.05

CD8+ (%) N 15 15 0.890

Mean 29.32 28.96

Standard Deviation 5.78 8.16

Minimum 22.91 13.77

Maximum 43.84 43.36

*Obtained using t-test for independent samples
Table 6 provides the descriptive statistics for immunological parameters of subjects in two groups at visit 1. The geometric mean for IgG spike in test group (546.59 SD: 6.84) was higher than placebo group (373.31 SD: 9.17); however, the difference was statistically insignificant (p=0.619). The other immunological parameters like CD3+, CD4+ and CD8+ also indicated statistically insignificant difference between the two groups with p-values 0.457, 0.743 and 0.890 respectively. The mean values were in the normal ranges in both the groups. Table 7: Distribution of subjects in two groups as per concomitant medication at VISIT 1

Treatment arm
Test (N=15) Placebo (N=15)
n % n %
Concomitant medication N 15 100.0% 15 100.0%
None of the patients in two groups required any concomitant medication at visit 1.
Table 8: Descriptive statistics for vital parameters of subjects in two groups at VISIT2

Treatment arm P-value*
Vital parameters Test Placebo

Pulse rate (/min) N 15 15 0.079

Mean 78.33 74.80

Standard Deviation 4.39 6.09

Minimum 72 64

Maximum 87 82

Respiratory rate (/min) N 15 15 0.999

Mean 19.40 19.40

Standard Deviation .91 .74

Minimum 18 18

Maximum 21 20

Temperature (oC) N 15 15 0.221

Mean 36.55 36.35

Standard Deviation .45 .43

Minimum 36.10 36.10

Maximum 37.20 37.20

Systolic BP (mmHg) N 15 15 0.481

Mean 115.33 114.00

Standard Deviation 5.16 5.07

Minimum 110 110

Maximum 120 120

Diastolic BP (mmHg) N 15 15 0.726

Mean 75.33 74.67

Standard Deviation 5.16 5.16

Minimum 70 70

Maximum 80 80

*Obtained using t-test for independent samples
Table 8 provides the descriptive statistics for vital parameters of subjects in two groups at visit 2. It is evident from the table that all the parameters showed statistically insignificant difference of means between the two arms (p > 0.05). Table 9: Distribution of subjects in two groups according to adverse events at VISIT 2

Treatment arm

Test (N=15) Placebo (N=15)

n % n %
Adverse No 15 100.0% 15 100.0%
event
Serious No 15 100.0% 15 100.0%
adverse
event
Table 9 shows that none of the patients in either groups had adverse or serious
adverse events at visit 2.
Table 10: Descriptive statistics for vital parameters of subjects in two groups at
VISIT3

Treatment arm P-value*
Vital parameters Test Placebo

Pulse rate (/min) N 15 15 0.527

Mean 79.33 78.13

Standard Deviation 4.51 5.68

Minimum 70 68

Maximum 84 88

Respiratory rate (/min) N 15 15 0.668

Mean 18.93 19.07

Standard Deviation .80 .88

Minimum 18 18

Maximum 20 20

Temperature (oC) N 15 15 0.418

Mean 36.60 36.73

Standard Deviation .43 .46

Minimum 36.10 36.10

Maximum 37.20 37.20

Systolic BP (mmHg) N 15 15 0.183

Mean 117.33 114.00

Standard Deviation 7.99 5.07

Minimum 110 110

Maximum 130 120

Diastolic BP (mmHg) N 15 15 0.754

Mean 76.00 75.33

Standard Deviation 6.32 5.16

Minimum 70 70

Maximum 90 80

*Obtained using t-test for independent samples

Table 10 provides the descriptive statistics for vital parameters of subjects in two groups at visit 3. Again, it is evident from the table that all the parameters showed statistically insignificant difference of means between the two arms (p > 0.05).
Table 11: Distribution of subjects in two groups according to physical examination status at VISIT3

Treatment arm
Physical parameters Test (N=15) Placebo (N=15)

n % n %
General appearance Normal 15 100.0% 15 100.0%
Skin Normal 15 100.0% 15 100.0%
Ear nose throat Normal 15 100.0% 15 100.0%
Head neck thyroid Normal 15 100.0% 15 100.0%
Heart Normal 15 100.0% 15 100.0%
Lung Normal 15 100.0% 15 100.0%
Chest Normal 15 100.0% 15 100.0%
Abdomen Normal 15 100.0% 15 100.0%
Extremities Normal 15 100.0% 15 100.0%
Genitelia Normal 15 100.0% 15 100.0%
Anorectal Normal 15 100.0% 15 100.0%
Lymph nodes Normal 15 100.0% 15 100.0%
Musculo skeletal Normal 15 100.0% 15 100.0%
Neurological Normal 15 100.0% 15 100.0%

Table 11 provides the description of physical examination status of patients at visit 3 in two study groups. All the 15 patients, in either group, had normal presentation on various physical examination parameters as shown in the table.
Table 12: Distribution of subjects in two groups according to adverse events at VISIT3

Treatment arm

Test (N=15) Placebo (N=15)

n % n 15
15 %
Adverse events No 15 100.0%
100.0%
Serious adverse events No 15 100.0%
100.0%
Table 12 shows that none of the patients in either groups had adverse or serious
adverse events at visit 3.
Table 13: Distribution of subjects in two groups as per concomitant medication

Treatment arm

Test (N=15) Placebo (N=15)

n % n 15 %
Concomitant medication No 15 100.0%
100.0%
at VISIT 3
None of the patients in two groups required any concomitant medication at visit 3.
Table 14: Descriptive statistics for vital parameters of subjects in two groups at VISIT4

Treatment arm P-value*

Test Placebo
Pulse rate (/min) N 15 15 0.222

Mean 81.80 79.33

Standard Deviation 4.60 6.10

Minimum 74 68

Maximum 90 89

Respiratory rate (/min) N 15 15 0.115

Mean 18.93 18.53

Standard Deviation .70 .64

Minimum 18 18

Maximum 20 20

Temperature (oC) N 15 15 0.903

Mean 36.33 36.35

Standard Deviation .34 .26

Minimum 36.00 36.10

Maximum 37.10 37.10

Systolic BP (mmHg) N 15 15 0.761

Mean 119.20 118.53

Standard Deviation 5.70 6.16

Minimum 110 110

Maximum 130 130
Diastolic BP (mmHg) N 15 15 0.818

Mean 77.73 77.27

Standard Deviation 5.06 5.91

Minimum 70 70

Maximum 86 90

*Obtained using t-test for independent samples
Table 14 provides the descriptive statistics for vital parameters of subjects in two groups at visit 4. Again, it is evident from the table that all the parameters showed statistically insignificant difference of means between the two arms (p > 0.05). Table 15: Distribution of subjects in two groups as per physical examination status at VISIT4

Physical examination Treatment arm

Test (N=15) Placebo (N=15)

n
15
15
15
15
15
15
15
15 % n
15
15
15
15
15
15
15
15 %
General appearance Normal
100.0%
100.0%
Skin Normal
100.0%
100.0%
Ear nose throat Normal
100.0%
100.0%
Head neck thyroid Normal
100.0%
100.0%
Heart Normal
100.0%
100.0%
Lung Normal
100.0%
100.0%
Chest Normal
100.0%
100.0%
Abdomen Normal
100.0%
100.0%

Extremities Normal 15 15 100.0% 15 15 100.0%
Genitelia Normal
100.0%
100.0%

Anorectal Normal 15 15 15 15 100.0% 15 15 15 15 100.0%
Lymph nodes Normal
100.0%
100.0%
Musculo skeletal Normal
100.0%
100.0%
Neurological Normal
100.0%
100.0%
Table 15 provides the description of physical examination status of patients at visit 4 in two study groups. All the 15 patients, in either group, had normal presentation on various physical examination parameters as shown in the table.
Table 16: Descriptive statistics for various haematological parameters in two groups at VISIT4

Treatment arm P-value*
Test Placebo

RBC (millions/mm3) N 15 15 0.075

Mean 4.85 4.45

Standard Deviation .62 .58

Minimum 3.74 3.57

Maximum 5.90 5.33

Haemoglobin (gm/dl) N 15 15 0.836

Mean 13.99 13.85

Standard Deviation 1.72 1.88

Minimum 10.04 9.93

Maximum 16.12 16.76

MCV (fl) N 15 15 0.157

Mean 88.31 93.12

Standard Deviation 8.45 9.63

Minimum 71.50 76.20

Maximum 102.30 111.00

MCH (pg) N 15 15 0.121

Mean 28.97 30.81

Standard Deviation 2.89 3.39

Minimum 23.00 23.50

Maximum 32.80 37.00

MCHC (g/dl) N 15 15 0.399

Mean 32.81 33.05

Standard Deviation .81 .77

Minimum 31.70 30.80

Maximum 34.60 34.00

Hematocrit N 15 15 0.348

Mean 42.65 40.37

Standard Deviation 5.11 7.70

Minimum 31.20 18.80

Maximum 47.80 50.10

Neutrophils (%) N 15 15 0.670

Mean 54.73 56.33

Standard Deviation 10.59 9.71

Minimum 36.00 39.00

Maximum 70.00 75.00

Lymphocytes (%) N 15 15 0.796

Mean 34.47 33.53

Standard Deviation 10.15 9.43

Minimum 20.00 18.00

Maximum 53.00 52.00

Monocytes (%) N 15 15 0.640

Mean 7.40 7.07

Standard Deviation 2.13 1.71

Minimum 4.00 5.00

Maximum 13.00 12.00

Eosinophils (%) N 15 15 0.687

Mean 3.40 3.07

Standard Deviation 2.44 2.02

Minimum 1.00 1.00

Maximum 8.00 7.00

Basophils (%) N 15 15 -

Mean .00 .00

Standard Deviation .00 .00

Minimum .00 .00

Maximum .00 .00

WBC (cells/mm3) N 15 15 0.763

Mean 6778.67 6947.33

Standard Deviation 1508.95 1529.95

Minimum 4900.00 5080.00

Maximum 10690.00 10010.00

Platelet N (10^3/ul) N 15 15 0.863

Mean 288.60 292.80

Standard Deviation 57.68 73.55

Minimum 193 150

Maximum 419 439

*Obtained using t-test for independent samples
Table 16 provides the descriptive statistics for haematological parameters of
subjects in two groups at visit 4. It is evident from the table that all the parameters
showed statistically insignificant difference of means between the two arms (p >
0.05).
Table 17: Descriptive statistics for biochemical parameters for subjects in two
groups at VISIT4

Treatment arm P-value*
Biochemical parameters Test Placebo

ALT (U/L) N 15 15 0.380

Mean 20.47 25.27

Standard Deviation 12.47 16.73

Minimum 8.00 8.00

Maximum 50.00 67.00

AST (U/L) N 15 15 0.259

Mean 21.20 24.80

Standard Deviation 7.36 9.62

Minimum 10.00 14.00

Maximum 39.00 47.00

Serum creatinine (mg/dl) N 15 15 0.657

Mean .87 .84

Standard Deviation .19 .17

Minimum .59 .63

Maximum 1.29 1.24

Bilirubin (mg/dl) N 15 15 0.421

Mean .55 .45

Standard Deviation .45 .20

Minimum .00 .18

Maximum 1.96 .88

*Obtained using t-test for independent samples
Table 17 provides the descriptive statistics for biochemical parameters of subjects
in two groups at visit 4. It is evident from the table that all the parameters showed
statistically insignificant difference of means between the two arms (p > 0.05).
Table 18: Descriptive statistics for immunological parameters in two groups at
VISIT4

Treatment arm P-value*
Test Placebo

IgG spike (BAU/ml) N 15 15 0.047

Geometric mean 535.14 91.37

Geometric SD 7.70 13.36

Minimum 15.99 0.40

Maximum 5140.44 2155.00

CD3+ (%) N 15 15 0.266

Mean 67.73 70.11

Standard Deviation 6.17 5.26

Minimum 57.84 60.03

Maximum 83.27 78.45

CD4+ (%) N 15 15 0.261

Mean 37.04 39.26

Standard Deviation 5.83 4.69

Minimum 27.36 30.98

Maximum 46.49 49.40

CD8+ (%) N 15 15 0.515

Mean 30.65 28.95

Standard Deviation 6.20 7.87

Minimum 23.01 15.10

Maximum 42.52 39.92

*Obtained using t-test for independent samples; P-value in bold indicates statistical significance.

Parameter Statistical parameter Test Placebo P-value*
Log IgG Difference N 15 15 0.024

Mean 0.98 0.24

SD 1.44 8.19

Minimum 0.59 0.008

Maximum 2.72 1.00

CD3+ Difference

Mean -0.25 0.20 0.776

SD 3.31 5.07

Minimum -5.18 -7.88

Maximum 5.89 6.75

CD4+ Difference

Mean -0.68 0.79 0.248

SD 3.85 2.87

Minimum -6.87 -4.31

Maximum 4.6 5.19

CD8+ Difference

Mean 1.33 -0.01 0.476

SD 3.51 6.27

Minimum -3.51 -15.38

Maximum 11.23 14.60

Table 18 provides the descriptive statistics for immunological parameters of subjects in two groups at visit 4. The geometric mean for IgG spike in test group (535.14 SD: 7.70 BAU/ml) was higher than placebo group (91.37 SD: 13.36); and the difference was statistically significant (p=0.047). The mean for CD3+ in test group (67.73 ± 6.17%) was smaller than placebo group (70.11 ± 5.26%); however, the difference was statistically insignificant (p=0.266). The mean for CD4+ in test group (37.04 ± 5.83%) was lower than that of placebo group (39.26 ± 4.69%); however, the difference was statistically insignificant (p=0.261). The mean for CD8+ in test group (30.65 ± 6.20%) was higher than that of placebo group (28.95 ± 7.87%); however, the difference of means was statistically insignificant (p=0.515).
Table 19: Descriptive statistics for change in immunological parameters between VISIT4 and VISIT1 in two groups
*Obtained using t-test for independent samples; Bold p-value indicate statistical significance
Table 19 provides the change in the immunological status of parameters between visit 4 and visit 1 (visit 4 – visit 1) in both the groups. As regards IgG spike, the mean log IgG difference in test group (0.98 SD: 1.44) was higher than that of placebo group (0.24 SD: 8.19); and the difference was statistically significant with a p-value of 0.024. For CD3+, the mean change in test group was -0.25 (SD: 3.31), while in placebo group was 0.20 (SD: 5.07). The difference between the means was statistically insignificant (p=0.776). Similarly, for CD4+, the mean change in test group was -0.68 (SD: 3.85), while in placebo group was 0.79 (SD: 2.87). The difference in the means was statistically insignificant (p=0.258). For CD8+, the mean change in test group was 1.33 (SD: 3.51), while in placebo group was -0.01 (SD: 6.27). The difference between the means was statistically insignificant (p=0.467). Table 20: Comparison of parameters between Visit 4 and Visit 1 in each group

Parameter Visit Mean (SD)

Test Placebo

IgG Visit 1 546.59 (6.84) 373.31 (9.17)

Visit 4 535.14 (7.70) 91.37 (13.36)

P-value* 0.824 0.021
CD3+ Visit 1 67.98 (4.77) 69.91 (8.67)

Visit 4 67.73 (6.17) 70.11 (5.26)

P-value* 0.773 0.881
CD4+ Visit 1 37.72 (7.23) 38.47 (5.00)

Visit 4 37.04 (5.83) 39.26 (4.69)

P-value* 0.505 0.308
CD8+ Visit 1 29.32 (5.78) 28.96 (8.16)

Visit 4 30.65 (6.20) 28.95 (7.87)

P-value* 0.164 0.993
*Obtained using paired t-test; Bold p-value indicate statistical significance; SD:
Standard deviation.
Table 20 shows the pair wise comparison of different markers between visit 1 and
visit 4. In test group, the mean difference of marker values between two time points
was insignificantly different than zero. In placebo group, there was a significant
reduction in the IgG values at visit 4, as indicated by a p-value of 0.021. The mean
difference of other three markers were insignificantly different than zero, as
indicated by p > 0.05.
In other words, in test group, all the parameters were almost maintained till visit 4;
however, in placebo arm, except IgG, the other three markers hardly deviated at
visit 4 compared to visit 1.
Table 21: Distribution of subjects as per categories of parameters in two groups

Treatment arm
Parameter Test (N=15) Placebo (N=15)

n % n %
CD3+ @ VISIT1 Within reference range 15 100.0% 12 80.0%

Below reference range 0 0.0% 1 6.7%

Above reference range 0 0.0% 2 13.3%
CD3+ @ VISIT4 Within reference range 14 93.3% 13 86.7%

Above reference range 1 6.7% 2 13.3%
CD4+ @ VISIT1 Within reference range 12 80.0% 14 93.3%

Below reference range 2 13.3% 0 0.0%

Above reference range 1 6.7% 1 6.7%
CD4+ @ VISIT4 Within reference range 15 100.0% 15 100.0%
CD8+ @ VISIT1 Within reference range 14 93.3% 12 80.0%

Below reference range 0 0.0% 2 13.3%

Above reference range 1 6.7% 1 6.7%
CD8+ @ VISIT4 Within reference range 15 100.0% 12 80.0%

Below reference range 0 0.0% 3 20.0%
CD3+ Reference range: 55-81%; CD4+ Reference range: 27-51%; CD8+ Reference range: 20.06-42.52
Table 21 gives the distribution of subjects as per categories of each parameter in two groups. The respective reference ranges for each parameter were used to classify patients as below, within and above range. At visit 1, in placebo group, there was 1 (6.7%) patient with CD3+ value below reference range; however, at visit 4, the patients had values either within or above reference range. For CD4+, in test group, there were 2 (13.3%) patients with values below range, while at visit 4, all patients in the group had values within range. As regards CD8+, in placebo group, 2 (13.3%) patients had values below range, and at visit 4, 3 (20.0%) patients had CD8+ values below reference range. In test group, all the patients had CD8+ values in reference range.

Table 22: Distribution of subjects in two groups according to adverse events at VISIT4

Treatment arm
Test (N=15) Placebo (N=15)

n % n %
Adverse events No 15 100.0% 15 100.0%
Serious adverse events No 15 100.0% 15 100.0%
Table 22 shows that none of the patients in either groups had adverse or serious adverse events at visit 4.
Table 23: Distribution of subjects in two groups as per concomitant medication at VISIT4

Treatment arm

Test (N=15) Placebo (N=15)

n % n %
Concomitant medication No 15 100.0% 15 100.0%
None of the patients in both the groups required concomitant medication at visit 4.
13. Summary
The four immunological markers IgG spike, CD3+, CD4+ and CD8+ were evaluated on subjects in both test and control groups at visit 1 and visit 4. At visit 1, the mean (geometric) concentration of IgG was higher in test group as compared to placebo group. The other parameters were similar and insignificantly different between two groups. At visit 4, for IgG, the difference of means between two groups was statistically significant. There was a significant reduction in the IgG levels in placebo group, while in test group, the mean concentration was almost retained. The other markers remained un-altered in both the groups at visit 4. In earlier study by Saleh MM (2020), the values of CD3+ and CD4+ were found lower in COVID-19 infected patients as compared to normal individuals, while that

of CD8+ were higher in such patients. In the present study, the mean values for CD3+, CD4+ and CD8+ were close to normal individuals, at both visit 1 and visit 4. When the % values of these parameters were compared between two groups at visit 4, CD3+ was within the reference range in 93.3% subjects from test group, as compared to 86.7% in placebo group (p=0.999). CD4+ was within reference range in all 100% of subjects in both the groups, while CD8+ was within reference range in 100% of subjects from test group and 80% of subjects from placebo group (p=0.224). For CD8+, the difference was insignificant due to small sample; however, was in favour of the test group. Also the finding on IgG was also in favour of the test group.

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Claims We claim
1. A herbo-mineral composition for immunomodulatory action comprising a combination of at least 10 – 12 herbomineral ingredients.
2. The herbo-mineral composition as claimed in claim 1 for enhancing immunity against infection of SARS-Cov-2.
3. The herbo-mineral composition as claimed in claim 1 wherein dose of each Herbal Medicine is reduced to 1% - 50 % of its regular dose.
4. The herbo-mineral composition as claimed in claim 1 wherein dose of each Herbal Medicine is reduced to 1% - 25 % of its regular dose.
5. The herbo-mineral composition as claimed in claim 1 wherein the composition comprises at least eight herbal medicines selected from Zingiber officinale, Embelia ribes, Glycyrrhiza glabra Withania somnifera, Terminalia chebula, Tinospora cordifolia, Emblica officinalis, Asparagus racemosus and Piper longum; and 1 or 2 minerals selected from Calcium, zinc, or combination thereof.
6. The herbomineral composition as claimed in claim 1 wherein the herbal medicines are in the form of Ghana or extract and the mineral is in incinerated form or bhasma form or salt form.
7. The herbomineral composition in any of the preceding claims having in a single dosage form Zingiber officinale from 30 - 60 mg, Embelia ribes from 50 – 62.5 mg, and Glycyrrhiza glabra from 30 – 50 mg, Withania somnifera from 50 – 75 mg, Terminalia chebula from 50 – 75 mg, Tinospora cordifolia from 37.5 – 62.5 mg, Emblica officinalis from 30 -60 mg, Asparagus racemosus 20 - 40 mg and Piper longum 0.025 -10 mg, zinc from 10 – 30 mg and calcium from 50-75 mg.
8. The herbomineral composition in any of the preceding claims having in a single or two dosage form Zingiber officinale from 60 - 120 mg, Embelia ribes from 100 – 125 mg, and Glycyrrhiza glabra from 60 – 100 mg, Withania somnifera from 100 – 150 mg, Terminalia chebula from 100 – 150 mg, Tinospora cordifolia from 75 – 125 mg, Emblica officinalis from 60 -

120 mg, Asparagus racemosus 40 - 80 mg and Piper longum 0.050 -20 mg, zinc from 20 – 60 mg and calcium from 100 – 150 mg.
9. The herbomineral composition according to any of the preceding claim in the form of a tablet, capsule, caplets, coated tablets, multi-layered tablets, minitablets, pill, powder, granules, seeds, pellet, extrudates, spheronized material, compacts, particulate preparation, dispersion, dispersible tablet, fast disintegrating tablet, lozenge, sublingual or buccal tablets, powder mixture, syrup, suspension, powder for oral solution, powder for oral suspension injectables, liquid, solution, subcutaneous, intravenous, intramuscular composition.
10. A process to prepare herbomineral composition according to any of the preceding claim comprising
iv) preparing Ghan form of one or more rasayana herbs from water /
aqueous extract or from super critical extraction process;
v) preparing Bhasma preparation of calcium and / or zinc wherein 90
% particles are below 50 µM, more preferably below 15 µM and most preferably below 1 µM. or Alternatively, preparing colloidal or nano particulate forms; and
vi) optionally mixing / blending ghan form and Bhasma form to prepare
herbomineral composition.