WO2003055558A1

WO2003055558A1 - Polyherbal composition for the treatment of bronchial asthma and the process

Info

Publication number: WO2003055558A1
Application number: PCT/IN2002/000041
Authority: WO
Inventors: Panchapagesa Muthuswamy Murali
Original assignee: Dalmia Center for Research and Development
Current assignee: Dalmia Center for Research and Development
Priority date: 2001-12-31
Filing date: 2002-03-12
Publication date: 2003-07-10
Anticipated expiration: 2004-06-30
Also published as: AU2002246307A1

Abstract

The present invention relates to a synergistic herbal composition for the treatment of bronchial asthma and a process for preparing the same. The said composition comprises the following herbs: Achyranthes aspera, Woodfordia furiticosa, Solanum xanthocarpum, Justicia adhatoda, Acacia arabica Zingiber officinalis, Syzygium aromaticum bud, Curcuma longa, Holarrhena antidysentercia, Enicostemma littorale, Calotropis procera, Piper longum, Piper nigrum and Elettaaria Cardamomum.

Description

POLYHERBAL COMPOSITION FOR THE TREATMENT OF BRONCHIAL ASTHMAAND THE PROCESS

Field of Invention This invention relates to a synergistic herbal composition for the treatment of bronchial Asthma and the process for preparing the same. Background of the invention

Asthma mer^~s a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils and T. lymphocytes. This inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly, at night and/ or in the early morning. These episodes are usually associated with widespread but variable air-flow obstruction i.e. often reversible either spontaneously or with treatment and these changes are associated with an increase in the existing bronchial hyper responsiveness to a variety of stimuli

For unknown reasons, the morbidity and mortality from asthma are increasing in many parts of the world, making it a global health concern. The heterogeneous nature of the clinical manifestations and therapeutic responses of asthma in both adult and pediatric patients indicate that it may be more of a syndrome rather than a specific disease entity. Numerous factors, including viral infections, allergen and irritant exposure, and exercise, among others, complicate both the short- and long-term management of asthma. Therapeutic intervention has focused on the appreciation that airway obstruction in asthma consists of bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucous secretion, and the influx of a variety of inflammatory cells. Indigenous and herbal medicines have been in use for many centuries in India for the treatment of bronchial asthma. For instance the following herbs and ingredients have been used either individually or in combination for heeling asthma: Ginger - Zingiber Officinale

Ginger supports a healthy cardiovascular system. Ginger makes blood platelets less sticky and less likely to aggregate. A powerful natural Expectorant, used widely in Chinese formulas, for coughs, colds, diarrhea, vomiting, and abdominal pains associated with colds, Edema (stagnation of fluids in lungs) and chronic bronchitis. The dried rhizome of ginger contains approximately 1—4% volatile oils. These are the medically active constituents of ginger, and they are also responsible for ginger characteristic odor and taste. The aromatic principles include zingiberene and bisabolene, while the pungent principles are known as gingerols and shogaols. The pungent constituents are credited with the anti nausea and anti vomiting effects of ginger. Piper Nigrum

Piper Nigrum acts as a powerful anti convulsant and natural anti inflammation agent. Piper longum

Piper Longum used in traditional practice to promote respiratory health. It significantly benefited respiratory function and builds up resistance against respiratory tract constriction and inflammation Piper longum also enhances thermogenic response, or release of metabolic heat energy. Elatteria cardamom Elatteria cardamom is a powerful natural anti inflammatory agent and analgesic with significant cardiotonic properties . It heals the inflammation of respiratory tract Cinnamomum cassia Cinnamomum Cassia has been used as a diaphoretic, antipyretic and analgesic . Enhances & eases Expectoration of fluids in Lungs. It has powerful anti Ede ic properties - prevention of stagnation of fluids in Lungs It is used as a carminative , purgative and astringent . It is very effective as a cardiac stimulant and diuretic for stimulation of liver i o functions

Adhatoda vasica or Malabar Nut

^■ Adhatoda Vasica is considered in the East to be the best possible treatment for all chest diseases. Used in herbal tobacco to relieve asthma

1 Adhatoda vasica has been traditionally used in the management of allergic disordersand bronchial asthma .

Research performed over the last three decades revealed that the alkaloids present in the leaves, vasicine and vasicinone, possess powerful respiratory stimulant activity . Cassia occidentalis

Cassia Occidentalis has Powerful Anti microbial and Anti spasmodic activity. The plant contains emodin, physcion, chrysophanol, sitosterol and a xanthone cassiolin

Solanum xanthocarpum The plant is employed for cough, asthma and pains in the ches .

The plant is also credited with diuretic properties and is used to cure dropsy . Very spiny diffuse herb with blue flowers and yellow, globose berries . Solasonine is present in the fruits. Solanum indicum

Traditionally used as Indian Ayurvedic Medicine for Asthma , dry & spasmodic cough and chest pains . Aegle marmelos

Aegle Marmelos has very powerful Cardiotonic properties strengthens the cardiac muscles and increases the force of contraction and expansion of cardiac muscles

A number of drugs are available in the market for the treatment of asthma but side effects limit their prolonged use.

Hence there was a need to develop safer alternatives, which is aimed to cure asthma, having a safety profile similar to that of placebo. Yet another object of the present invention is to minimize rather reduce the usage of any steroid drug and to develop an effective herbal composition for the treatment of bronchial asthma.

To achieve the said objective this invention provides a synergistic herbal composition for the treatment of bronchial asthma, said composition comprising the following herbs indicated in the proportions given below:

Ingredients : Proportions ( by wt%

Achyranthes aspera 15.5% - 17.5% Woodfordia furiticosa 1 1.5% - 13.6 % Solanum xanthocarpum 1 1.5 % - 13.6 % Justicia adhatoda 1 1.5 % - 13.6 % Acacia arabica : 1 1.5 % - 13.6 %

Zingiber officinal is : 3.6 % - 4.94%

Syzygium aromaticum bud : 3.6 % - 4.94 %

Curcuma longa : 3.6 % - 4.94 % Holarrhena antidysentercia : 3.6 % - 4.94 %

Enicostemma littorale : 2.22 % - 3.3 %

Calotropis procera : 2.22 % - 3.3 %

Piper longum : 2.22 % - 3.3 %

Piper nigrum : 8.2 % - 7.8 % Elettaaria Cardamomum : 0.06 % - 0.19 %

The said herbal composition comprises the following herbs by weight %:

Achyranthes aspera : 16.62 %

Woodfordia furiticosa : 12.2 % Solanum xanthocarpum : 12.2 %

Justicia adhatoda : 12.2%

Acacia arabica : 12.2%)

Zingiber officinalis : 4.15 %o

Syzygium aromaticum bud : 4.15 % Curcuma longa : 4.15 %)

Holarrhena antidysentercia : 4.15 %o

Enicostemma littorale : 3.17 %o

Calotropis procera : 3.17 %o

Piper longum : 3.17 %) Piper nigrum : 8.33%)

Elettaaria Cardamomum : 0.15 %

The said herbal composition comprises the following herbs by weight %>: Achyranthes aspera : 17.33%

Woodfordia furiticosa : 12.72%

Solanum xanthocarpum : 12.72%

Justicia adhatoda : 12.72%

Acacia arabica : 12.72%

Zingiber officinal is : 4.32%

Syzygium aromaticum bud 4.32%

Curcuma longa : 4.32%

Holarrhena antidysentercia : 4.32%

Enicostemma littorale : 3.30%

Calotropis procera : 3.30%

Piper longum 3.30%

Piper nigrum : 8.70%

Elettaaria Cardamomum : 0.15%

The said herbal composition comprises the following herbs by weight:

Achyranthes aspera : 700-950 mg

Woodfordia furiticosa : 600-700 mg

Solanum xanthocarpum : 600-700 mg

Justicia adhatoda : 600-700 mg

Acacia arabica : 600-700 mg Zingiber officinalis : 160-300 mg

Syzygium aromaticum bud : 160-300 mg

Curcuma longa : 160-300 mg

Holarrhena antidysentercia : 160-300 mg Enicostemma littorale 100-200 mg Calotropis procera 100-200 mg Piper longum 100-200 mg Piper nigrum 350-500 mg Elettaaria Cardamomum 3-12 mg

The parts of the herbs used in said composition are:

Achyranthes aspera : root

Woodfordia furiticosa : flower

Solanum xanthocarpum : fruit

Justicia adhatoda : leaves

Acacia arabica : bark

Zingiber officinalis rhizome

Syzygium aromaticum bud : flower bud

Curcuma longa : rhizome

Holarrhena antidysentercia : seed

Enicostemma littorale : Whole plant

Calotropis procera : root

Piper longum : fruit

Piper nigrum : fruit

Elettaaria Cardamomum : fruit

This invention further provides a process of preparing synergistic herbal composition for the treatment of bronchial Asthma comprising:

shade drying the following herbs, Achyranthes aspera, Woodfordia furiticosa, Solanum xanthocarpum, i Justicia adhatoda, Acacia arabica, Zingiber officinalis, Syzygium aromaticum bud, Curcuma longa, Holarrhena antidysentercia, Enicostemma littorale, Calotropis procera. Piper longum, Piper nigrum and Elettaaria Cardamomum

mixing the said dried herbs in the following proportions to yield the formulation for extraction

Ingredients : Proportions ( by wt%

Achyranthes aspera : 15.5% - 17.5%

Woodfordia furiticosa : 11.5% - 13.6 %

Solanum xanthocarpum : 11.5 % - 13.6 % Justicia adhatoda : 11.5 % - 13.6 %

Acacia arabica : 11.5 % - 13.6 %

Zingiber officinalis : 3.6 % - 4.94%

Syzygium aromaticum bud : ^■ 3.6 % - 4.94 %

Curcuma longa : 3.6 % - 4.94 % Holarrhena antidysentercia : 3.6 % - 4.94 %

Enicostemma littorale : 2.22 % - 3.3 %

Calotropis procera : 2.22 % - 3.3 %

Piper longum : 2.22 % - 3.3 %

Piper nigrum : 8.2 % - 7.8 % Elettaaria Cardamomum : 0.06 % - 0. 19 %

racting the said herbs collectively with food, grade alcohol, - filtering the extract,

- condensing the said formulation and drying,

- powdering the dried formulation, sieving, and packing in four capsules to be consumed on a single day.

The said filtration is carried out through cloth followed by Whatman filter paper (no. 1 ) by applying vacuum pressure.

The condensation is carried out by using Rotovac vacuum pump at 650 mm pressure and at temperature 45 °C.

The extraction of herbs is carried out for a minimum period of 18 hours.

The invention will now be described with reference to the accompanying drawings and following examples:

Figure 1 is a graph, which illustrates the Peak Expiratory Flow Rate measured in all the patients as shown in Table 1.

Figure 2 is a graph, which illustrates the Forced Expiratory Volume in one second measured in all the patients as shown in Table 2.

Figure 3 is a graph, which illustrates Forced Vital Capacity of the lung in Liters which measured in all the patients as shown in Table 3 every week Figure 4: is a graph which illustrates the Forced Expiratory Flow Rate 25-75% of the Forced Vital Capacity which measured in all the patients as shown in Table 4 every week.

5 Example 1:

Shade dried or the fresh materials are used for processing depending on the protocol. All herbs were collectively extracted. Extraction of all herbs were carried out with food grade alcohol (70% V/V) in a Soxhlet 10 apparatus for a minimum of 18 hrs. The extracts were filtered through cloth, followed by Whatman filter paper (no. 1 ) by applying vacuum pressure.

The herbs are mixed in the following proportion by weight for 15 extraction.

Achyranthes aspera : 872 mg

Woodfordia furiticosa : 640 mg

Solanum xanthocarpum : 640 mg

20 Justicia adhatoda : 640 mg

Acacia arabica : 640 mg

Zingiber officinalis 217.6 mg

Syzygium aromaticum bud : 217.6 mg

Curcuma longa : 217.6 mg .5 Holarrhena antidysentercia : 217.6 mg

Enicostemma littorale : 166.4 mg

Calotropis procera 166.4 mg

Piper longum : 166.4 mg Piper nigrum : 436.8 mg

Elettaaria Cardamomum : 7.68 ma

After extraction the formulation is further condensed using a Rotovac vacuum pump at 650 mm pressure and at temperature 45°C. Completely dried material is then scrapped, powdered and sieved. The sieved drug is packed in four capsules and given to a patient for single days dosage. This sieved drug is referred to as DCBT 4567.

In-patients with asthma, DCBT 4567 has demonstrated significant reduction in cough, sputum, rales rhonchi and improves pulmonary functions. The knowledge gained from this study would be of many thousands of subjects, who, like yourself, may suffer from asthma.

CLINICAL TRIAL

Patients are allocated in equal proportions to Herbal, Bio Medical or to Placebo series using random sampling numbers.

The period of treatment will be 24 weeks. A total of 7 days grace period is allowed for completion of treatment after first 4 weeks of continuous treatment. The daily dosage is given in Capsules which contains DCBT 4567 herbal drug (1.6 gm) of the herbal extract or Salbutamol (12 mg) or Ragi

2.1 powder (Placebo). The trial drugs are administered orally in a capsule with warm water after taking food. All drugs - Herbal, Bio Medical and Placebo - are supplied in capsules of same size, shape, colour and appearance, so that neither the doctor nor the patient is aware of whether an individual patient is prescribed Herbal treatment or Bio Medical treatment or the Placebo.

Drugs are packaged separately for each patient and supplied to the investigators. The trial centers supply the drugs to the patients once a week.

TRIAL RESULTS

DCBT4567 - ASTHMA - TRIAL RESULTS

Table 1

Peak Expiratory Flow Rate was measured in all of them every week. A 15% improvement in this value since the time the patient entered in the trial was used as an indication for improvement

Table 2

Forced Expiratory Volume in one second was measured in all of them every week. A 15% improvement in this value since the time the patient entered in the trial was used as an indication for improvement.

Table

Forced Vital Capacity of the lung in Liters was measured in all of them every week. A 15% improvement in this value since the time the patient entered in the trial was used as an indication for improvement. Table 4:

Forced Expiratory Flow Rate 25-75% of the Forced Vital Capacity was measured in all of them every week. A 15% improvement in this value since the time the patient entered in the trial was used as an indication for improvement.

ASTHMA TRIAL

Initially, as per the protocol, the trial period is only 13 weeks. As the patients and the physicians are comfortable with the trial drugs, the trial period might be extended up to 17 weeks. Total no of patients inducted in the trial 90

Patients dropped within one week 2

Patients dropped/irregular/no follow up till 13 weeks 6

Patients dropped/irregular/no follow up till 17 weeks 13 CHARACTERISTICS OF PATIENTS ADMITTED

(88 PATIENTS)

IMPROVEMENT IN FEVl/FVC RATIO SHOWN BY THE PATIENTS IN THE TRIAL

Distribution of Patients to Number of Weeks of Additional Drug Intake

It is evident that the herbal composition is very effective in the treatment of Asthma.

Percentage reduction in no. of patients

The Clinical symptoms of Asthma are Dysponea, Wheezing, Cough and Rhonchi. The patients treated with the herbal medicine DCBT have shown significant improvement when treated for Asthma.

DCBT 4567 - COMPLAINTS DURING TREATMENT

Claims

We claim:

1. A synergistic herbal composition for the treatment of bronchial asthma, said composition comprising the following herbs indicated in the proportions given below:

Ingredients Proportions (by wt%) Achyranthes aspera 15.5%- 17.5% Woodfordia furiticosa 11.5%- 13.6% Solanum xanthocarpum 11.5%- 13.6% Justicia adhatoda 11.5%- 13.6% Acacia arabica 11.5%- 13.6% Zingiber officinalis 3.6 % - 4.94% Syzygium aromaticum bud 3.6 % - 4.94 % Curcuma longa 3.6% -4.94% Holarrhena antidysentercia 3.6% -4.94% Enicostemma littorale 2.22 % 1 -I

% Calotropis procera 2.22 % J.J Vo Piper longum 2.22 % - 3.3 % Piper nigrum 8.2 % - 7.8 % Elettaaria Cardamomum 0.06% -0.19%

2. A composition as claimed in claim 1, wherein the following herbs used are the following proportions by weight %:

Achyranthes aspera : 16.62%

Woodfordia furiticosa : 12.2%

Solanum xanthocarpum : 12.2%

Justicia adhatoda : 12.2%

Acacia arabica : 12.2%

Zingiber officinalis : 4.15% Syzygium aromaticum bud 4.15 %

Curcuma longa 4.15 %

Holarrhena antidysentercia 4.15 %

Enicostemma littorale 3.17 %

Calotropis procera 3.17 %

Piper longum 3.17 %

Piper nigrum 8.33%

Elettaaria Cardamomum 0.15 %

10 3. A composition as claimed in claim 1 wherein the following herbs used are the following proportions by weight %:

Achyranthes aspera 17 33%

Woodfordia furiticosa 12 72%

Solanum xanthocarpum 12 72%

15 Justicia adhatoda 12 72%

Acacia arabica 12 72%

Zingiber officinalis 4.32%

Syzygium aromaticum bud 4.32%

Curcuma longa 4.32%

Holarrhena antidysentercia 4.32%

Enicostemma littorale 3.30%

Calotropis procera 3.30%

Piper longum J . 0%

Piper nigrum : 8.70%

T Elettaaria Cardamomum : 0.15%

4. A composition as claimed in claim 1 wherein the following herbs used are the following proportions by weight

"5? Achyranthes aspera : 700-950 mg

Woodfordia furiticosa : 600-700 mg

Solanum xanthocarpum : 600-700 mg

Justicia adhatoda : 600-700 mg Acacia arabica : 600-700 mg

Zingiber officinalis : 160-300 mg

Syzygium aromaticum bud : 160-300 mg

Curcuma longa : 160-300 mg

Holarrhena antidysentercia : 160-300 mg Enicostemma littorale : 100-200 mg_.

Calotropis procera : 100-200 mg

Piper longum : 100-200 mg

Piper nigrum : 350-500 mg

Elettaaria Cardamomum : 3-12 mg

5. A composition as claimed in claim 1 wherein the following herbs used are the following proportions by weight

Achyranthes aspera : 872 mg

Woodfordia furiticosa : 640 mg Solanum xanthocarpum : 640 mg

Justicia adhatoda : 640 mg

Acacia arabica : 640 mg

Zingiber officinalis : 217.6 mg

Syzygium aromaticum bud : 217.6 mg Curcuma longa : 217.6 mg

Holarrhena antidysentercia : 217.6 mg

Enicostemma littorale : 166.4 mg

Calotropis procera : 166.4 mg Piper longum : 166.4 mg

Piper nigrum : 436.8 mg

Elettaaria Cardamomum : 7.68 mg

6. A composition as claimed in claim 1 wher ein the parts of the herbs used in said composition are:

Achyranthes aspera : root

Woodfordia furiticosa flower

Solanum xanthocarpum : fruit

Justicia adhatoda leaves

Acacia arabica : bark

Zingiber officinalis : rhizome

Syzygium aromaticum bud : flower bud

Curcuma longa rhizome

Holarrhena antidysentercia : seed

Enicostemma littorale : Whole plant

Calotropis procera : root

Piper longum : fruit

Piper nigrum : fruit

Elettaaria Cardamomum fruit

7. A process of preparing synergistic herbal composition for the treatment of bronchial Asthma as claimed in claim 1 comprising: shade drying the following herbs, Achyranthes aspera, Woodfordia furiticosa, Solanum xanthocarpum. Justicia adhatoda, Acacia arabica, Zingiber officinalis, Syzygium aromaticum bud, Curcuma longa, Holarrhena antidysentercia, Enicostemma littorale, Calotropis procera. Piper longum, Piper nigrum and Elettaaria Cardamomum mixing the said dried herbs in the following proportions to yield the formulation for extraction Ingredients : Proportions (by wt% )

Achyranthes aspera : 15.5% - 17.5%

Woodfordia furiticosa : 11.5% - 13.6 %

Solanum xanthocarpum : 11.5 % - 13.6 %

Justicia adhatoda : 11.5 % - 13.6 % Acacia arabica : 11.5 % - 13.6 %

Zingiber officinalis : 3.6 % - 4.94%

Syzygium aromaticum bud : 3.6 % - 4.94 %

Curcuma longa : 3.6 % - 4.94 %

Holarrhena antidysentercia : 3.6 % - 4.94 % Enicostemma littorale : 2.22 % - 3.3 %

Calotropis procera : 2.22 % - 3.3 %

Piper longum : 2.22 % - 3.3 %

Piper nigrum : 8.2 % - 7.8 %

Elettaaria Cardamomum : 0.06 % - 0. 19 % - extracting the said herbs collectively with food grade alcohol,

- filtering the extract,

- condensing the said formulation and drying,

8. A process as claimed in claim 7 wherein said filtration is carried out through cloth followed by Whatman filter paper (no. 1) by applying vacuum pressure.

9. A process as claimed in claim 7 wherein said condensation is carried out by using Rotovac vacuum pump at 650 mm pressure and at temperature 45 °C.

10. A process as claimed in claim 7 wherein said extraction of herbs is carried out for a minimum period of 18 hours.