Integrative Medicine Case Reports, Volume 5, Issue 1 (January), 2024

A Randomized, Open-Label, Controlled Clinical Study to Evaluate the Efficacy of Guduchi Pindi in the Management of Anjananamika

N. Ramya,* Naveen B.S., Geethakumari B.

¹Department of PG Studies in Shalakya Tantra, Sri Sri College of Ayurvedic Science and Research Hospital, Bengaluru, Karnataka, India

Introduction

Sarvendriyanam Madhye Nayanasya Pradhanatvam (1). Of all the senses that human beings are equipped with, the eyes are considered as the foremost. The eyes are perhaps the most expressive part of the face, giving a good indication of how a person is feeling. Acharya Vagbhata clearly mentioned that, we should make an effort to safeguard our eyes throughout our lives because, for a blind person, day and night are the same regardless of their wealth (2). Therefore, it is important to maintain the health of the eyes. But, due to various reasons, the eyes are affected by numerous disorders. Anjananamika is one of the Vartmagata (eyelid disorder), Raktapradhana (mainly have a pathology stemming from Rakta), Sadhya netra vikaras (treatable disorder of eye) (3). According to Acharya Sushrutha, the signs and symptoms of Anjananamika are Daha (burning sensation), Toda (pricking sensation), Tamra Pitaka (coppery red swelling) which are Mridu (soft) with Manda Ruja (mild pain) (4).

The symptoms resemble nodular swelling on the eyelid. A stye, which is also known as a hordeolum, is a common condition involving the eye seen in ophthalmology and general medicine OPDs. It is a painful, acute infectious condition that primarily affects the sebaceous glands of the upper or lower eyelid. A hordeolum typically manifests as a little pustule around the edge of the eyelid (5).

One of the most prevalent kinds of eyelid lesions observed in the ophthalmology clinic is chalazion. It is a chronic, lipogranulomatous inflammatory lesion brought on by the Meibomian gland obstruction, with a prevalence rate of 0.57% or 5,686/million population (6). Chalazia occur as a result of meibomian gland malfunction and mechanical blockage, which causes stasis and prevents sebum from being released. A painless lump inside the eyelid or at the edge of the lid is the typical presentation of this subacute to chronic illness (6).

Management of Anjananamika in Ayurveda classics consists of Swedana, Bhedana and Pratisarana. Pindi is chosen as it is a form of Chikitsa where the medications are placed on the eyelids for a longer duration. It works by absorbing substances through the transdermal route. Since the appendages are not notably present over the eye lid skin, the thinner stratum corneum of the eye lid skin indicates lower resistance, which may be the cause of higher drug absorption through the eye lid skin. The majority of absorption happens through the skin (7). In the present clinical study, Guduchi Pindi is taken as trial group and Nimbadi Pindi is taken as control group. Nimba and Lodhra, used as the control, both have Chakshushya and Krimighna properties. Guduchi, used as the trial, also has Chakshushya and Krimihara, along with Kandughna and Dahaprashamana properties.

Saranya M. S and Pradeep Kumar K. A comparative study to evaluate the efficacy of Manashiladi Vidalaka and Nimbadi Pindi in Anjananamika (External Hordeolum). 40 patients
registered for the study were randomly allocated to two groups A and B with 20 patients each. Within the group analysis shows that both the groups have highly significant results i.e., progressive decrease in symptoms. The comparative analysis between the groups showed no significant results except for Kandu (p = 0.047). Yuvraj Sutar, Ajitkumar S Herwade, Late Kedari Redekar. To study efficacy of Rasanjantrikatu lepa on Anjannamika with special reference to Hordeolum externum. Total 60 patients were selected for study. Two groups, 30 patients in each group having Lakshanas of Anjananamika were selected. Though significant relief provided by drugs of both groups, in Lakshanas like Kandu (itching), the Rasanjan-trikatu Lepa turns more effective.

The primary Objective of the study was to evaluate the efficacy of Guduchi Pindi in the management of Anjananamika based on treatment outcome related to swelling, pain, burning sensation, itching and pricking sensation and thereafter, to re-evaluate the efficacy of Nimbadi Pindi in the management of Anjananamika based on treatment outcome related to swelling, pain, burning sensation, itching and pricking sensation. The secondary objective of the study was to compare the efficacy of Guduchi Pindi with that of Nimbadi Pindi in the management Anjananamika.

Methods

Study design

Study type is a Randomized comparative clinical study, the timing was prospective. Masking was open label, and grouping was double arm. Randomization was done by lottery method and group intervention method was parallel. The nature of the study was explained to each subject in detail and informed consent was taken.

Participants

(a) Inclusion Criteria:

Subjects presenting with the classical features of Anjananamika as described under diagnostic criteria. Subjects between the ages of 21 and 60, regardless of gender, occupation, religion, socioeconomic background, or duration of illness. Subjects willing to participate with written informed consent, which is conveyed in the language which the subject can understand.

(b) Exclusion Criteria:

Subjects suffering from

1. Blepharitis

2. Eyelid tumours

3. Eyelid swelling dues to any trauma

4. Eyelid swelling due to systemic causes

Assessment criteria

Signs and symptoms of Anjananamika are evaluated.

SUBJECTIVE PARAMETERS

Grading of subjective parameters of assessment criteria

4) Numeric Pain Rating Scale (8)

A respondent chooses a whole number (0–10 integers) on the NPRS, a segmented numerical version of the visual-analog scale (VAS), that most accurately represents the degree of their pain.

0 – No pain at all

10 – As bad as it can be

Showing Numeric Pain Rating Scale (8)

Objective parameters

1. Measurement of the swelling with vernier callipers.

SAMPLE SOURCE

30 patients, aged 21 to 60 years, of both genders, who met the diagnostic requirements were chosen from the OPD and IPD of the Sri Sri College of Ayurvedic Science & Research Hospital in Bengaluru. They were divided into two equal groups, A and B. Every patient provided their informed permission.

Drug source

Guduchi Pindi: (Trial drug) The Guduchi Patra were procured from herbal garden of Sri Sri College of Ayurvedic Science & Research Hospital. The fresh leaves of Guduchi (10g) were crushed and made into a Kalka using a Khalva Yantra. It was then be wrapped in a gauze piece.

Nimbadi Pindi: (Control drug) Nimbadi Pindi consists of two ingredients – Nimba Patra and Lodhra. Nimba Patra were procured from herbal garden of Sri Sri College of Ayurvedic Science & Research Hospital, while Lodhra Churna was obtained from a GMP certified company (Pavaman pharmaceuticals, GMP Lic. No: AUS-895, Batch No – CH-721). Nimba Patra were collected freshly for each procedure. Fresh leaves of Nimba were crushed and made into a Kalka using a Khalva Yantra. The powder of Lodhra was made into Kalka by adding water. Equal quantity of both Kalkas (5g each) was wrapped in a gauze piece.

Interventions

Results

Numbers randomized – 15 subjects randomized to each group. Recruitment – 30 subjects Numbers analysed – 15 subjects in Group-A and 14 subjects in Group-B were analysed.

Outcome

Daha

Table 1: Daha at various intervals (Data: Median, 25th, and 75th percentiles of data).

In Group A and group B, right eye and left eye no statistically significant change was observed on D3, D5, D10 and D15 (Table 1). Thus, Both the Groups, i.e.: A and B had no statistically significant difference in Daha. Comparison shows that the difference between the groups was statistically non – significant on all points of time i.e.; D3, D5, D10 and D15.

Kandu

Table 2: Kandu at various intervals (Data: Median, 25th, and 75th percentiles of data).

Only one subject in Group B left eye, had Grade 0 Kandu on D0, had grade 1 Kandu on D3, which again came down to Grade 0 on D5, D10 and D15. It was not considered for statistics. Group A right eye – showed statistically significant decrease in Kandu on D15. Group A left eye – showed statistically significant decrease in Kandu on D5, D10 and D15.

Group B right eye – no statistically significant change could be observed on D3, D5, D10 and D15 Group B left eye – shows statistically significant decrease in Kandu on D5, D10 and D15. Comparison shows that the difference between the groups was statistically non – significant on all points of time i.e.; D3, D5, D10 and D15 (Table 2).

Toda

Table 3: Toda at various intervals (Data: Median, 25th, and 75th percentiles of data).

Group A right eye – showed statistically significant decrease in Toda on D3, D5, D10, D15. Group A left eye – no statistically significant change could be observed on D3, D5, D10 and D15. Group B right eye – no statistically significant change could be observed on D3, D5, D10 and D15

Group B left eye – shows statistically significant decrease in Toda on D10 and D15. Comparison shows that the difference between the groups was statistically non – significant on all points of time i.e.; D3, D5, D10 and D15 (Table 3).

Ruja

Table 4: Ruja at various intervals (Data: Median, 25th, and 75th percentiles of data).

Only one subject in Group A left eye, had Grade 0 Ruja on D0, Grade 2 Ruja on D3, Grade 3 on D5, Grade 2 Ruja on D10, which again came down to Grade 0 on D15. It was not considered for statistics. Group A right eye – showed statistically significant decrease in Ruja on D3, D5, D10, D15. Group A left eye – showed statistically significant decrease in Ruja on D10, D15.

Group B right eye – no statistically significant change could be observed on D3, D5, D10 and D15. Group B left eye – no statistically significant change could be observed on D3, D5, D10 and D15. Comparison reveals that at all time points (D3, D5, D10, and D15), the difference between the groups was statistically non-significant (Table 4).

AREA OF BASE OF THE SWELLING

Table 5: Area at various intervals (Data: Median, 25th, and 75th percentiles of data)

Group A right eye – showed statistically significant reduction in Area of base of the swelling on D10, D15. Group A left eye – showed statistically significant reduction in Area of base of the swelling on D3, D5, D10, D15.

Group B right eye – showed statistically significant reduction in Area of base of the swelling on D3, D5, D10, D15. Group B left eye – showed statistically significant reduction in Area of base of the swelling on D10, D15.

Comparison shows that the difference between the groups was statistically non – significant on all points of time i.e.; D5, D10 and D15 (Table 5).

Effect size difference

Effect size difference (ESD) on Friedman Test for repeated measures was calculated using W = Q/n (k-1)

Effect size difference (ESD) on Mann-Whitney test with 95% confidence limit was calculated using r = Z/√N ±1.96/√N

Effect size difference (ESD) on Mann Whitney test with 95% of confidence limit was calculated using r = Z/√N ± 1.96/√N < 0.1 – Small; <0.3 – Medium; >0.5 – Large; >0.8 – Very Large

Overall assessment

Effect size is found to be small which is clinically significant in favour of Group A.

Discussion

The maximum number of subjects in this clinical trial, that is, 76.67% (23) belonged to the age group of 21–30 years, followed by 20% (6) belonged to the age group of 31–40 years, while 3.33% (1) belonged to the age group of 41–50 years and no subjects were in 51–60 years age group. There incidence of stye is the said to be slightly higher in subjects of 30–50 years of age, whereas for chalazion, it is 21–30 years of age (5,6).

This could be because the people in Madhyama Vaya have more Pradhanya of Pitta, and have a higher tendency to develop the related disorders. Anjananamika is a Raktaja condition. Due to the Ashraya Ashrayee Bhava of Rakta and Pitta, we can consider that Anjananamika has a higher incidence in Madhyama Vaya. Maximum number of subjects, that is, 56.67% (17) were students, followed by 10% each of therapists (3), home makers (3) and people with administrative work/desk jobs (3) and 3.33% of subjects being farmer (1), beautician (1), doctor (1), cook (1). The incidence of chalazion is said to be highest in students. The predisposing factors for Anjananamika include eye strain, which is probably seen more in students, when compared to those of other professions, leading to a higher
incidence.

Maximum number of subjects, that is, 73.33% (22) had Anjananamika on the upper eyelid, whereas 26.67% (8) had it in the lower eyelid. The glands of the eyelids are present more in the upper eyelid than in the lower eyelids. Pathologies in these glands are a major cause for eyelid swellings, therefore leading to a higher incidence in the upper eyelids (9). Pindi is a procedure where preparation is told to be placed on a strip of cloth, which has to be placed on the eyes of the subjects. Detailed explanation regarding the time duration has not been explained in the Ayurveda classics. In the present study, the duration was fixed as per the control group (10). Pindi acts through the transdermal pathway of absorption because it is applied externally to the eye lids. Because the stratum corneum of the eye lid skin is thinner, it exhibits lower resistance, which may account for the increased drug penetration through it. Over the skin of the eye lid, the appendages are not notably visible. The epidermal pathway accounts for the majority of absorption (7). In Guduchi Pindi, the fresh leaves of Guduchi were pounded into a Kalka, and in Nimbadi Pindi, the fresh leaves of Nimba were ponded, added with Lodhra Churna along with water is added to make a proper Kalka. Hence, in both preparations, the medium is water. Hydrophilic absorption happens through intra cellular domain and enters into the micro circulation. That is, medial and the lateral palpebral arteries forming the arterial arcades of eye lids. Thus, the medicine reaches the target.

Sorption of a penetrant molecule on the surface layer stratum corneum.

↓

Diffusion through it and viable epidermis and finally it reaches dermis.

↓

The molecule enters the microcirculation and spreads throughout the body.

Daha may have reduced by the Pitta and Raktahara properties of Guduchi and its presence in Daha Prashamana Gana (11–13). Guduchi has chemical constituents including alkaloids (tinosporine, magnoflorine) sesquiterpenoids, phenolics, which have anti-inflammatory action, which may have helped in reduction of Daha (14–18). Daha may have reduced by the qualities of Sheeta Veerya, Pitta Raktanut of Nimba and Lodhra, Apakvam pachayet shopham quality seen in Nimba. Nimba has chemical constituents including azadirachtin, gedunin, nimbolide, triterpenoids which have anti-
inflammatory actions (19,20). Lodhra, has chemical constituents including alkaloids, flavonoids, tannins, phenols, which have anti-inflammatory action, which may have helped in reduction of Daha (21–26). Kandu may have reduced by the Kandughna and Tridoshahara properties of Guduchi. Guduchi has chemical constituents including alkaloids, sesquiterpenoids, phenolics, which have anti-microbial action, which may have helped in reduction of Kandu.

Kandu may have reduced by the Kandughna and Shleshmasrapittanut properties of Nimba, Kaphapitta, Raktahara properties of Lodhra. Nimba has chemical constituents including azadirachtin, gedunin, nimbolide, triterpenoids which have anti-microbial actions Lodhra, has chemical constituents including alkaloids, flavonoids, tannins, phenols, which have anti-microbial action, which may have helped in reduction of Kandu. Toda and Ruja may have reduced by the Ushna Veerya and Tridoshahara properties of Guduchi. Guduchi has chemical constituents including alkaloids, sesquiterpenoids, phenolics, which have anti-
inflammatory and analgesic action, steroids like giloinsterol, ß-Sitosterol, which may have helped in reduction of Toda and Ruja.

Toda and Ruja may have reduced by the Tridosha as well as Asranut properties of Nimba and Lodhra Nimba has chemical constituents including azadirachtin, gedunin, nimbolide, triterpenoids which have anti-inflammatory actions Lodhra, has chemical constituents including alkaloids, flavonoids, tannins, phenols which have anti-inflammatory action, which may have helped in reduction of Toda and Ruja. Swelling may have reduced by the Tridoshahara, Krimihara properties of Guduchi. Guduchi has chemical constituents including alkaloids, sesquiterpenoids, phenolics, which have anti-inflammatory and anti-microbial action, which may have helped in reduction of swelling Swelling may have reduced by the Vrananut, Apakvam Pachayet Shopham, Vranam Pakvam Vishodhayet, Vrana and Shopha Shantaye, Asrk and Pittanut properties of Nimba and Shophanashana, Asranut proprerties of Lodhra. Nimba has chemical constituents including azadirachtin, gedunin, nimbolide, triterpenoids which have anti-inflammatory, anti-proliferative actions Lodhra, has chemical constituents including alkaloids, flavonoids, tannins, phenols which have anti-inflammatory, anti-microbial and anti-ulcer actions, which may have helped in reduction of swelling.

Conclusion

Anjananamika is one of the commonly seen eyelid disorders. It is more common in children and young adults (though no age is bar). Anjananamika is one of the Vartmagata, Raktapradhana, Sadhya netra vikaras. Majority of subjects had Anjananamika in the upper eyelid. In the present study no adverse drug reaction was reported thus no rescue medications were given. Guduchi has Rakta and Pittahara properties, and is also present in the Daha Prashamana Gana, due to which it may have reduced Daha. Kandu may have reduced due to its Kandughna and Tridoshahara properties, whereas Toda and Ruja may have reduced by its Ushna Veerya and Tridoshahara properties. Swelling may have reduced by the Tridoshahara, Krimihara properties of Guduchi.

Nimbadi Pindi may have shown reduction in Daha by the qualities of Sheeta Veerya, Pitta Raktanut of both the drugs and Apakvam pachayet shopham quality seen in Nimba. Reduction in Kandu may have been by the Kandughna and Shleshmasrapittanut properties of Nimba, Kaphapitta, Raktahara properties of Lodhra. Toda and Ruja may have reduced by the Tridosha as well as Asranut properties of Nimba and Lodhra. Swelling may have reduced by the Vrananut, Apakvam Pachayet Shopham, Vranam Pakvam Vishodhayet, Vrana and Shopha Shantaye, Asrk and Pittanut properties of Nimba and Shophanashana, Asranut proprerties of Lodhra. All the Dravyas used in the study are Chakshusya, and may have helped in the general betterment of the condition.

Pindi is an external treatment in which the medication is applied to the eyelids using a strip of cloth, known as gauze. It works by absorbing substances through the transdermal route. Since the appendages are not notably present over the eye lid skin, the thinner stratum corneum of the eye lid skin indicates lower resistance, which may be the cause of higher drug absorption through the eye lid skin. The majority of absorption happens through the skin. The effects of the treatment within the groups were assessed based on Friedman Repeated Measures Analysis of Variance on Ranks, One Way Repeated Measures Analysis of Variance test. Between the group assessment was done by Mann-Whitney rank sum test and paired t test.

Based on effect size difference, Group B showed better result than Group A clinically. When we compare the overall changes in between the Groups, Group B (90.91%) showed better result than Group A (70.53%), but statistically non-significant with p Value >0.05, which shows that alternate hypothesis is rejected and null hypothesis (H0), that is, “Guduchi Pindi and Nimbadi Pindi have equivalent effect in management of Anjananamika.” is accepted.

Trial registration

The study was prospectively recorded in CTRI with registration number – CTRI – CTRI/2022/09/045173, dated: 2-09-2022.

Authors’ contribution

NR: collected data, analyzed the data, and wrote the manuscript; NBS, GB, Conceptualization, study design, Editing.

Source of funding

None.

Conflict of interest

No conflict of interest.

Received Date: 15-12-23: Revised Date: 27-1-24
Accepted Dated: 29-1-24

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