sg phyto pharma private limited, kolhapurfree iron is toxic to cells as it acts as a catalyst in the...

S.G. Phyto Pharma Private Limited, Kolhapur 2016

SGPPPL/Limiron Granules Clinical Trial Concise Report 1

SG PHYTO PHARMA PRIVATE LIMITED, KOLHAPUR

CLINICAL TRIAL REPORT

Evaluation of Limiron Granules in pregnancy as a source of

Iron & Calcium and effect on birth outcome Conducted at

BHARATI VIDYAPEETH DEEMED UNIVERSITY

College of Ayurveda, Hospital & Research Center

Dhanakawadi, Pune 411043

Principal Investigator: Dr. (Mrs.) Swati S. Mohite

Head,Department of Prasuti avum Stree Roga

College of Ayurveda, Hospital & Research Center,

Dhanakawadi, Pune Phone: 020-24371723 Fax: 020-24365289



BHARATI VIDYAPEETH DEEMED UNIVERSITY

BHARATI VIDYAPEETH AYURVEDA COLLEGE , HOSPITAL & RESEARCH CENTER

Department of Prasutitantra & Streeroga

Katraj Dhankawadi Pune 411043

Investigation Team

Sr. No. INVESTIGATOR NAME DESIGNATION

1 Principal

Investigator

Dr. ( Mrs) S. S. Mohite Professor & Head

Dept. of Prasutitantra & Streeroga

2 Co- Investigator Dr. M. B. Kulkarni Lecturer


3 Co- Investigator Dr. A. S. Patil Lecturer


4 Co-Investigator Dr. K. P. Pawar Lecturer


5 Physician Dr. Sorte Honorary Physician

6 Physician Dr. Ghare Associate Professor

Dept. of Kayachikitsa

7 Statistician Mr. Abhay Joshi College of Ayurveda

8 Scientist Dr. Anita Killari IRSHA (Interactive Research School

for Health Sciences, BVDU, Pune)

Duration of Trial:

1: Period for recruitment of patient : One & Half Year

2: Period for data collection : Six months

3: Period for data analysis : Six months

Introduction:

� According to science pregnancy is a not a pathological condition but physiologically different

condition than normal, for fetal & maternal nourishment so special care is to be taken to

achieve this goal. It is therefore very important to nourish a pregnant woman by supplying

additional micronutrients. Researchers have proved that it is a phase of oxidative stress and

hence it is very essential to provide micronutrients as well as antioxidants with routine diet.

� World Health Organization (WHO) recommends regular intake of iron & calcium during

pregnancy to avoid fetal & maternal complications so iron & calcium preparations with essential

micronutrients are given from fourth months till sixth week after delivery. During pregnancy,

these medicines are prescribed for daily consumption for a long period. If iron & calcium are

given together, calcium inhibits iron absorption.



� Here in this study both iron & calcium are given together as it has been reported that when

taken with food, CaCO3 DOES NOT INHIBIT THE ABSORPTION OF FeSO4 (Nutri. Res. News

letter,March, 1991).

� Mandoor bhasma & Kukkutandtwak bhasma are rich sources of iron & calcium. They provide Fe

& Ca in biological form. Hence the absoption & bioavailability is better than pure iron & calcium

compounds.

� The findings of the studies carried out at National Institute of Virology, Pune, by Dr. R. P. Deokar

& others have clearly shown the best bioavailability of both against their poor absorption from

synthetic salts. It is also found during this, that Limiron granules have improved general

performance during reproduction , lactation & normal growth which was confirmed by birth

weight & weaning weight of experimental animals & litter size.

� Limiron Granules contain Kukkutandtwak bhasma (Processed Eggshell powder) containing

CaCO3 (2%) along with Mandur bhasma (0.3% Fe) in ferrous form. Mostly, since Madur bhasma

is processed in Triphala & Maka kadha it is converted in to a complex that does get interfered by

Calcium. Limiron granules also contain Shatavari a natural anabolic, which helps in building body

tissue. The study has been done on Shatavari for the fulfillment of post graduate curriculum

which had shown significant increase in birth weight.

� In this study birth outcome record correlate its relation in both groups.

Moreover, observations on humans & animals with Limiron Granules for over two decades have

revealed High Nutritional status.

Aims & Objectives

Primary objective: To study efficacy of Limiron Granules in pregnant woman in maintaining

haemoglobin & serum calcium.

Secondary objective: To study side effects & to evaluate birth outcome.

Clinical Study

Place:

1. Clinical work : Bharati Ayurved Hospital, Pune

2. Laboratory work : 1. Bharati Ayurved Hospital, Pune

2. Nishkarsh Laboratory, Pune

3. IRSHA, Bharati University, Pune



Study Design:

Materials & Methods: Limiron Granules

Sr. No. Name of Ingredient Scientific name Quantity

1 Shatavari Root Powder Asparagus racemosus 200 mg

2 Kukkutandatwak Bhasma Ayurvedic Generic Preparation

(Processed egg shell powder)

250 mg

3 Mandur Bhasma Ayurvedic Generic Preparation

(Processed Ferrioxidum)

100 mg

4 Bhuikohala Tuber powder Ipomoea digitata 100 mg

5 Khajur Phoenix sylvestris 150 mg

6 Sugar Pharma grade sugar Q.S. to 5 gm

Permitted colours & flavours added

Route of administration : Oral

Dose : 5 gm, twice/day, with meal

Mandur shuddhi – Triphala kadha in gomutra, Maka bhavana

Methodology:

1) Sample size: 121 pregnant cases (including dropouts) Final size: 100

2) Inclusion criteria:

1. 14 to 20 weeks of pregnancy

2. Nutritional anemia

3) Exclusion criteria:

1. Any chronic illness

2. Abnormal TFT

3. GI bleeding

4. Liver disorders

5. Gout

6. Renal stone

4) Discontinuation criteria:

1. Drastic fall in Hemoglobin level and serum calcium levels after two months.



5) Assessment criteria:

Objective parameters-

� Investigations at 14 – 20 weeks of pregnancy (recommended by WHO):

No Investigation 20 Wk 32wks 40wks

1 Haemogram ESR Yes

2 HbSAg Yes

3 V D R L Yes

4 B S L – R Yes

5 Blood group Yes

6 Liver Function Tests. Yes

7 Urine – R/ M Yes

8 Ultrasonography Yes Yes Yes

� Investigations for correlation of efficacy of LIMIRON Granules (for one patient)

No. Investigations 14-20 wk 20 wk 24 wk 28 wk 32 wk 38 wk or

at labour

Purperal

6th

wk

1 Haemoglobin Yes

Yes

Yes

Yes

Yes

Yes

2 Haemogram with

ESR

Yes

2 Serum ferretin Yes

Yes

3 Serum calcium Yes

Yes

Yes

Yes

6) Period of treatment :

Minimum- 2 months

Maximum – 6 months

7) Period of follow up : 6- 8 months

8) Statistical analysis : Influential statistics & appropriate test applied according to data

SGPPPL/Limiron Granules Clinical Trial Concise Report

-----------------------------------------------------------------------------------------------------------------------------

No of visit

Recruited Drop

out

First visit

121 -

Second visit

118 3

Third visit

118 0

Fourth visit

110 8

Fifth visit

109 1

Sixth visit

107 2

Seventh visit

100 7

To evaluate the efficacy of Limiron Granules in pregnancy for maternal as well as foetal nutrition by evaluating haemoglobin &

serum calcium & its relation to birth outcome .

Inclusion criteria: 14 to 20 weeks of pregnancy, Nutritional anemia.

Exclusion criteria: Any chronic illness. ,Abnormal TFT, GI bleeding ,Liver disorders, Gout, Renal stone.

Discontinuation criteria: calcium levels after two months.

Data Analysis / Inference /

S.G. Phyto Pharma Private Limited, Kolhapur


FLOW CHART

-----------------------------------------------------------------------------------------------------------------------------

Data of drop out patient

Drop

out

Reason Other treatment

- -

3 Follow up failure – 3

0

8 Mild Hypertension- 3

Follow up failure – 5

Mild hypertension

Antihypertensive started

1 Haemoglobin drop-1 Intravenous iron infusion

given

2 Haemoglobin drop- 3 Intravenous iron infusion

given

7 Follow up failure

evaluate the efficacy of Limiron Granules in pregnancy for maternal as well as foetal nutrition by evaluating haemoglobin &

serum calcium & its relation to birth outcome .

14 to 20 weeks of pregnancy, Nutritional anemia.

Any chronic illness. ,Abnormal TFT, GI bleeding ,Liver disorders, Gout, Renal stone.

Objective criteria

Discontinuation criteria: Drastic fall in Hemoglobin level and serum calcium levels after two months.

Data Analysis / Inference / Conclusion


6

----------------------------------------------------------------------------------------------------------------------------------------

Other treatment

Mild hypertension –

Antihypertensive started

Intravenous iron infusion

Intravenous iron infusion

evaluate the efficacy of Limiron Granules in pregnancy for maternal as well as foetal nutrition by evaluating haemoglobin &

14 to 20 weeks of pregnancy, Nutritional anemia.

Any chronic illness. ,Abnormal TFT, GI bleeding

fall in Hemoglobin level and serum



RESULTS:

FIGURE 1. EFFECT OF LIMIRON GRANULES ON HB%

In India, anaemia is directly or indirectly responsible for 40 per cent of maternal deaths. There is 8 to 10-

fold increase in MMR when the Hb falls below 5 g/dl. Early detection and effective management of

anaemia in pregnancy can contribute substantially to reduction in maternal mortality. Maternal anaemia

is associated with poor intrauterine growth and increased risk of preterm births and low birth weight

rates. This in turn results in higher perinatal morbidity and mortality, and higher infant mortality rate. A

doubling of low birth weight rate and 2 to 3 fold increase in the perinatal mortality rates is seen when

the Hb is <8 g/dl. Intrauterine growth retardation and low birth weight inevitably lead to poor growth

trajectory in infancy, childhood and adolescence and contribute to low adult height.

� Consistent trend observed in Hb % level

� After 32nd

week, levels raised till delivery

� Slight decrease in Hb % level observed after delivery

Conclusion:

Limiron granules maintained the level of Hb % throughout the trial period. In absence of any other

medicine, only Limiron granules were given to the subjects and it was noted that the Hb% was found

maintained as same as it was at the time of enrollment.

� Mandur bhasma in Limiron Granules was found effective in maintaining the Hb% levels.

10.60 10.6210.10 9.93

10.6810.01

0

2

4

6

8

10

12

14

20 24 28 32 38/at labour Puerperal 6

week

Ha

em

og

lob

in (

%)

Labour week

Haemoglobin %



FIGURE 2. EFFECT OF LIMIRON GRANULES ON SERUM FERRITIN LEVEL

Ferritin is an ubiquitous intracellular protein that stores iron and releases it in a controlled fashion

Ferritin is a globular complex consisting of 24 protein subunits and is the primary intracellular iron-

storage protein, keeping iron in a soluble and non-toxic form. Ferritin is an indirect marker of the total

amount of iron stored in the body; hence serum ferritin is used as a diagnostic test for iron deficiency

anemia.

Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen

species. The ferritin levels measured usually have a direct correlation with the total amount of iron

stored in the body.

� Normal range in women : 4.63-204 ng/ml

� Ferritin levels at week 20 and 28 were maintained.

� Being one of the markers of iron deficiency anemia, week 28 readings were considered to assess

the significance of Limiron Granules in maintaining the levels of Ferritin.

� Hence, further assessment was not done

Conclusion:

It can be concluded from these findings that, serum Ferritin was found increased in week 28 when

compared to week 20.

� Mandur bhasma in Limiron Granules was found effective in maintaining the Ferritin levels

24.4731.04

0

10

20

30

40

50

60

70

20 Week 28 Week

Se

rum

Fe

reti

nin

ng

/ml

Labour week

Serum Ferritin



Figure 3: EFFECT OF LIMIRON GRANULES ON SERUM CALCIUM LEVEL

There are biological limits to a pregnant woman’s capacity to increase calcium absorption, and if she

does not consume adequate amounts of dietary calcium, she may be at increased risk for gestational

complications, such as preeclampsia and preterm delivery or long-term morbidities, such as excessive

bone loss. Calcium balance studies are typically used to determine if calcium intake is adequate to meet

requirements, but this technique has limitations. Calcium supplementation has shown effectiveness in

reducing the risk of preterm delivery in women with low calcium intakes.

� Normal range: 9.0-10.5 mg/dl

� Serum calcium levels have been found maintained during the course of treatment from week 20

to week 32.

� From week 20 to week 24 there was no significant increase in Ca level, but after 24 weeks, Ca

levels were found increased significantly at the end of week 32.

Conclusion: It can be concluded from these findings that, serum calcium levels were found increased

from week 20 to week 32 during the trial period.

� Kukkutandatwak bhasma in Limiron Granules was found effective in increasing the calcium

levels.

8.8

9

9.2

9.4

9.6

9.8

10

10.2

10.4

20 Week 24 Week 32 Week

Se

rum

Ca

lciu

m (

mg

/dl)

Labour Week

Serum Calcium


FIGURE 4. EFFECT OF LIMIRON GRANULES ON OXIDATIVE STRESS LEVELS (MDA



FIGURE 4. EFFECT OF LIMIRON GRANULES ON OXIDATIVE STRESS LEVELS (MDA- MALONDIALDEHYDE)


10

MALONDIALDEHYDE)



Reactive oxygen species degrade polyunsaturated lipids, forming malondialdehyde. This compound is a

reactive aldehyde and is one of the many reactive electrophile species that cause toxic stress in cells and

form covalent protein adducts referred to as advanced lipoxidation end-products (ALE), in analogy to

advanced glycation end- products (AGE).

The production of this aldehyde is used as a biomarker to measure the level of oxidative stress.

Oxidative stress occurs whenever the balance between the production of reactive oxidizing species

(ROS) and the antioxidant defense is disrupted.

In pregnancy, as a part of respiratory adaptation, there is triggering of aerobic environment that favours

oxidative stress. An imbalance due to increased lipid peroxidation and decreased antioxidant levels

leads to complications of pregnancy. During labour, oxidative stress increases several fold because of

the repeated uterine contractions leading to ischemia: this is followed by reperfusion, resulting in

increased production of ROS. The resultant stress, during spontaneous vaginal delivery is, in turn,

influenced by neural and hormonal factors in addition to pain, anxiety, fear and duration of labor.

� Before treatment and cord blood were measured for MDA levels.

� No significant changes were noted in both the groups.

� Oxidative stress was found to be restricted in comparison.

Conclusion:

It can be concluded that, MDA levels were not altered by the intake of Limiron granules. Throughout the

pregnancy, MDA levels and related oxidative stress was not altered. Maintained MDA levels indicates

less maternal and fetal complications which was observed in the study.

13.53

13.56

13.5

13.55

13.6

Before Treatment Cord blood

MD

A l

ev

el

pm

ol/

mg

MDA level pmol/mg



FIGURE 5: EFFECT OF LIMIRON GRANULES ON BIRTH OUTCOME

WHO recommends 15% of Caesarean Section as acceptable as far as Indian scenario is concerned.

Considering the facts and figures from Hb levels, there is a direct relation of low Hb and C-section.

Anemic condition hampers the normal delivery and worsens the conditions. Health supplements

containing iron, calcium and maintained blood pressure reduce the chances of Caesarean route.

However, Mild pre-eclampcia and eclampcia have increased the rates of Caesarean delivery rates.

� Out of 100 cases under trial, 83 undergone vaginal birth and had normal deliveries.

� 17% C sections were noted, but only Limiron Granules were advised as Iron, calcium

supplement. It suggests that only Limiron granules can help reduce the chances of C section

deliveries and moreover, increases the chances of normal births.

Conclusion: Indian rate for C section has revealed the increasing trend but as far as these

observations are noted, 83% of normal birth is promising.

Shatavari is well known uterine tonic, which gave strength to the uterus. Thus incidences of vaginal

delivery observed more in the study.

83

17

0

10

20

30

40

50

60

70

80

90

100

Normal Caesarian

Birth Outcome



FIGURE 6. EFFECT OF LIMIRON GRANULES ON MATURITY RATE

Pregnancy induced anemia and premature birth has strong co relation. Lowered Hb levels have shown

to increase the number of premature births, also planned caesarean deliveries. In such cases of

premature cases, most are caesarean. Full term normal delivery is very important in the future life of

new born. Comparative studies have revealed that the full term normal delivered babies are stronger

and have better immune response compared to pre term babies.

� 84 cases were observed for full term deliveries.

� Only 16 cases were noted for premature cases in which clinical conditions were considered for

caesarean mode.

� Pre term cases undergone caesarean sections due to low birth weight (<2000 gm).

� Full term deliveries were normal except 3 cases (2 caesareans for low liquor and 1 caesarean

due to 4000 gm baby weight).

Conclusion: It can be concluded that Limiron granules could help nourish the foetal growth and full term

maturity was observed in 84%. Limiron granules were found effective in full term normal delivery as well

as baby weight.

16

84

0

10

20

30

40

50

60

70

80

90

Pre term (34-36 weeks ) Full term

No

. o

f S

ub

ject

s

Maturity Rate



Figure 7: Effect of Limiron granules on birth weight (gm)

Limiron granule contains macro and micro nutrients which help in weight gain of the baby in the womb.

Out of 100 pregnant cases, 77 cases had full term normal deliveries. Remaining 23 had either premature

normal or premature C-section deliveries.

� In cases of full term normal deliveries, average baby weight was 2.600 kg. Gaining good birth

weight is considered as one of the prime importance in pregnancy.

Conclusion: Limiron granule provides all the essential micro and macro nutrients to both mother and

baby.

2.6

0

0.5

1

1.5

2

2.5

3

Average Birth Weight (Kg)



Figure 8: Effect of Limiron granules on Breast milk secretion

Limiron Granules contains Shatavari root powder, which is a renowned remedy used since ancient times

as a galactogogue. However, this phenomenon is subjective and cannot be quantified in terms of

secretion. Here, in this trial it was studied on the basis of whether the secretion is adequate or

moderate.

� The adequate secretion was noted in 93 mothers while only 7 reported moderate secretion.

� Adequacy measured by asking questions to mother while feeding.

Conclusion:

Shatavari root powder in Limiron granules has proved its efficacy in milk secretion as well as in

overall nourishment during pregnancy. Thus Limiron Granules were found effective as natural

galactogogue.

93

7

0

10

20

30

40

50

60

70

80

90

100

Adequate Moderate

No

. o

f su

bje

cts

Breast milk secretion


This document is sole property of S.G. Phyto Pharma Private Limited, Kolhapur.

Any part of this document is not to be reproduced in any form like Xerox, Images, Prints

MDA levels associated with Oxidative stress were found with no

significant alteration in the cord blood

compared with before treatment blood

samples

Adequate breast milk secretion in 93

mothers while on 7 showed moderate

secretion

Average baby weight for full term normal delivery was 2.6 kg



EXECUTIVE SUMMARY

This document is sole property of S.G. Phyto Pharma Private Limited, Kolhapur.

Any part of this document is not to be reproduced in any form like Xerox, Images, Prints, Reports etc. without written consent of

S.G. Phyto Pharma Private Limited, Kolhapur.

Limiron Granules could maintain the

Hb % levels throughout, even

after delivery Calcium levels were found maintained

from week 20-week 32

Ferritin levels were found maintained

from week 2028

Maturity rate was significantly higher in

terms of Pre term (<36 weeks) and full term

delivery

Birth outcome was significantly higher in terms of normal (83)

and caesarean sections (17)

MDA levels associated with Oxidative stress were found with no

significant alteration in

compared with before

Average baby weight for full term normal delivery was 2.6 kg


16

without written consent of

Calcium levels were found maintained

week

Ferritin levels were found maintained

from week 20- week 28

Maturity rate was significantly higher in

terms of Pre term (<36 weeks) and full term

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