A PHARMACEUTICAL KIT FOR ALLEVIATING ADVERSE EFFECTS OF CHEMOTHERAPY

FIELD

The present disclosure relates to a pharmaceutical kit. Particularly, the present disclosure relates to a pharmaceutical kit for alleviating adverse effects of chemotherapy, and improving immunomodulatory response and quality of life.

Abbreviations

WBC: White blood cells.

SGOT: Serum glutamic oxaloacetic transaminase.

SGPT: Serum glutamic pyruvic transaminase.

RSR: Respective survival rate

QoL: Quality of Life

QLQ C 30: Quality of Life Questionnaire.

Definitions

As used in the present disclosure, the following terms are generally intended to have the meaning as set forth below, except to the extent that the context in which they are used indicate otherwise.

Suvarna bhasma: The term “Suvarna bhasma” refers to “incinerated gold” prepared by incinerating gold in accordance with the present disclosure. The term “Suvarna bhasma” referred in the present disclosure is not the same, as used in the Ayurveda. Suvarna refers to 24 carat gold.

Mouktik bhasma: The term “Mouktik bhasma” refers to “incinerated pearl”, natural or cultured, prepared by incinerating pearl in accordance with the present disclosure. The term “Mouktik bhasma” referred in the present disclosure is not the same, as used in the Ayurveda.

Guduchi Sattva: The term “Guduchi Sattva” refers to extract comprising mainly starch of Tinospora cordifolia/sinensis/crispa/glabra prepared by alcoholic, hydro-alcoholic or aqueous extraction method. The term “Guduchi Sattva” referred in the present disclosure is not the same, as used in the Ayurveda.

Padmak: The term “Padmak” refers to “Lotus/Nelumbo nucifera”.

Durva: The term Durva refers to “Burmuda grass/Cynodon dactylon”.

Ananta: The term Ananta refers to “Swallow root (Decalepis hamiltonii) or Hemidesmus indicus or Cryptolepis buchnani or Ichnocarpus frutescens.”

Ghrut: The term “Ghrut” refers to “clarified butter” or “Cow's Ghee”.

Shankha bhasma: The “Shankha bhasma” refers to “incinerated Conch shell”. The term “Shankha bhasma” referred in the present disclosure is not the same, as used in the Ayurveda.

Shouktik bhasma: The term “Shouktik bhasma” refers to “incinerated empty pearl shell”. The term “Shouktik bhasma” referred in the present disclosure is not the same, as used in the Ayurveda.

Kapardika bhasma: The “Kapardika Bhasma” refers to “incinerated Cowries”. The term “Kapardika Bhasma” referred in the present disclosure is not the same, as used in the Ayurveda.

Pravala bhasma: The “Pravala Bhasma” refers to “incinerated coral”. The term “Pravala Bhasma” referred in the present disclosure is not the same, as used in the Ayurveda.

Shudhha Gairik: The “Gairik” is a natural clay earth pigment which is a mixture of ferric oxide and varying amounts of clay and sand. “Shudhha Gairik” refers to “processed Gairik”, prepared by roasting Gairik in ghee obtained from cow's milk. The term “Gairik” referred in the present disclosure is not the same, as used in the Ayurveda.

Vati: The term “Vati” refers to a method of medicine preparation in which herbs, minerals, and metallic compounds are compressed into tablet form.

Wick test: The term “wick test” refers to igniting a wick made out of residual solid part after separating Ghrut. Crackling sound of ignited wick indicates presence of water.

Trituration: The term “trituration” refers to either reducing the particle size of a substance or production of a homogeneous material by mixing component materials thoroughly or wet grinding any material with a liquid media like fresh juice or decoction etc.

Karnofsky score: The term “Karnofsky score” refers to the Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment

Symptom score: Symptom score of QLQ is indicative of symptomatology; hence decrease in symptom score represents both decrease in disease related symptoms and adverse effects of conventional treatment.

Function score: Functional score of QLQ signifies status of routine physical activities. Increase in functional scores represents improvement in QoL.

Global score: Global score of QLQ represents overall well-being of a patient. Increase in global scores represents improvement in QoL.

BACKGROUND

The background information herein below relates to the present disclosure but is not necessarily prior art.

By definition, chemotherapy includes the treatment of disease by means of chemicals that destroy cancerous tissue (anticancer therapy) or that have a specific toxic effect upon the disease producing microorganisms (antibiotics). This treatment modality produces favorable outcome in various cancers and bacterial diseases. However, it also produces generalized toxic effects such as nausea, vomiting, diarrhoea, fever, fatigue, skin discoloration, rigours, and the like, reduces immune response, increases oxidative stress, and hampers the quality of life, predominantly in cancers.

Breast cancer is a common malignancy in women worldwide. It ranks second to cervical cancer among cancers in females in India. The burden of breast cancer is increasing in both developed and developing countries. An increasing trend in incidence of breast cancer in India is reported from various registries of the National Cancer Registry Programme of the Indian Council of Medical Research.

The primary treatment for breast cancer is surgery. Surgery is often followed by chemotherapy. Chemotherapy is used to reduce the primary tumour load as well as recurrence and metastasis. Chemotherapy induces adverse side effects which are mainly caused by the inability of chemotherapeutic drugs to distinguish between dividing cancer cells and normal cells leading to increase in oxidative stress and hampered immune status. The other main adverse side effects include nausea, vomiting, loss of appetite, diarrhoea, constipation, weakness, alopecia (loss of hair), and early/late manifestations such as hepatotoxicity, renal toxicity and neurological problems. The early adverse side effects interfere with patient compliance and result in poor quality of life of patients. Further, the side effects such as myelo-suppression and liver and bladder toxicities may require discontinuation of therapy itself.

Efforts have been made to overcome these side effects by using alternative or adjunct therapies. However, these therapies used so far did not show effective reduction in the side effects.

Therefore, there is felt a need to provide a selected combination of herbo mineral and metallic compositions, in the form of a kit, that mitigates the aforestated problems.

OBJECTS

Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:

An object of the present disclosure is to ameliorate one or more problems of the prior art or to at least provide a useful alternative.

Another object of the present disclosure is to provide a pharmaceutical kit.

Still another object of the present disclosure is to provide a pharmaceutical kit for alleviating adverse effects of chemotherapy.

Another object of the present disclosure is to provide a pharmaceutical kit for reducing oxidative stress in patients administered with chemotherapy.

Yet another object of the present disclosure is to provide a pharmaceutical kit for improving the immune response in patients administered with chemotherapy.

Still another object of the present disclosure is to provide a pharmaceutical kit for improving the quality of life in patients administered with chemotherapy.

Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY

The present disclosure provides a pharmaceutical kit comprising a first container containing Suvarna Bhasmadi Vati (SBD) in a solid dosage form, a second container containing Mouktikyukta Kamdudha Vati (MKD) in a solid dosage form, a third container containing Padmakadi Ghrut (PDG) in a thick, viscous form, and a fourth container containing Ananta vati in a solid dosage form.

The SBD comprises Suvarna bhasma in an amount ranging from 2 wt % to 7 wt % of the total weight of the SBD, Mouktik bhasma in an amount ranging from 20 wt % to 35 wt % of the total weight of the SBD, Guduchi sattva in an amount ranging from 45 wt % to 60 wt % of the total weight of the SBD and at least one excipient in an amount ranging from 5 wt % to 30 wt % of the total weight of the SBD. In accordance with an embodiment of the present disclosure, the SBD comprises Suvarna bhasma in an amount ranging from 3 wt % to 5 wt % of the total weight of the SBD, Mouktik bhasma in an amount ranging from 23 wt % to 30 wt % of the total weight of the SBD, Guduchi sattva in an amount ranging from 48 wt % to 54 wt % of the total weight of the SBD, and at least one excipient in an amount ranging from 10 wt % to 25 wt % of the total weight of the SBD.

In an exemplary embodiment of the present disclosure, the SBD comprises Suvarna bhasma in an amount of 4.22 wt % of the total weight of the SBD, Mouktik bhasma in an amount of 26.37 wt % of the total weight of the SBD, Guduchi sattva in an amount of 52.74 wt % of the total weight of the SBD and gum acacia in an amount of 16.67 wt % of the total weight of the SBD.

The MKD comprises Mouktik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shankha bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shouktik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Kapardik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Praval bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Guduchi sattva in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shudhha Gairik in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, and at least one excipient in an amount ranging from 10 wt % to 30 wt % of the total weight of the MKD. In an exemplary embodiment of the present disclosure, the MKD comprises equal quantities of Mouktik bhasma, Shankha bhasma, Shouktik bhasma, Kapardik bhasma, Praval bhasma, Guduchi sattva and Shudhha Gairik i.e. 12 wt % each, and at least one edible binder, typically a natural gum, in an amount of 16 wt % of the total weight of the MKD.

The PDG comprises extracts of Padmak, Durva and Ananta dissolved or dispersed in cow's ghee.

PDG comprises an extract of petals and stalks of Nelumbo nucifera in an amount ranging from 13 wt % to 20 wt % of the total weight of the composition; an extract of whole plant of Cynodon dactylon in an amount ranging from 13 wt % to 20 wt % of the total weight of the composition; a decoction of roots of Decalepis hamiltonii in an amount ranging from 13 wt % to 20 wt % of the total weight of the composition; and cow's ghee in an amount ranging from 40 wt % to 60 wt % of the total weight of the composition.

In an exemplary embodiment of the present disclosure, PDG contains extract of petals and stalks of Nelumbo nucifera is in an amount of 16.66 wt % of the total weight of the composition; the extract of whole plant of Cynodon dactylon is in an amount of 16.66 wt % of the total weight of the composition; the decoction of roots of Decalepis hamiltonii is in an amount of 16.66 wt % of the total weight of the composition; and the clarified butter is in an amount of 50 wt % of the total weight of the composition.

The Ananta Vati comprises powder obtained from dried roots of Ananta in an amount ranging from 75 wt % to 92 wt % of the total weight of the Ananta Vati, wherein the powder has a particle size in the range of 150 to 180 microns, and at least one excipient in an amount ranging from 8 wt % to 25 wt % of the total weight of the Ananta Vati. The Ananta is Decalepis hamiltonni.

The compositions of SBD, MKD, and Ananta Vati are prepared in the form of solid unit dosage form selected from the group consisting of tablet, pill, and capsule.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING

The present disclosure will now be described with the help of the accompanying drawing, in which:

FIG. 1A and FIG. 1B depict the results of clinical investigation for anorexia, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 1B;

FIG. 2A and FIG. 2B depict the results of clinical investigation for nausea, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 2B;

FIG. 3A and FIG. 3B depict the results of clinical investigation for vomiting, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 3B;

FIG. 4A and FIG. 4B depict the results of clinical investigation for constipation, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 4B;

FIG. 5A and FIG. 5B depict the results of clinical investigation for fever, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 5B;

FIG. 6A and FIG. 6B depict the results of clinical investigation for taste alteration, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 6B;

FIG. 7A and FIG. 7B depict the results of clinical investigation for mucositis, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 7B;

FIG. 8A and FIG. 8B depict the results of clinical investigation for fatigue, wherein Study group is denoted by ‘X’ and Control group is denoted by ‘Y’. Low degree adverse effect is denoted by ‘P’ and High degree adverse effect is denoted by ‘Q’ in FIG. 8B;

FIG. 9 depicts a graphical representation of Haemogram showing haemoglobin level of Study group and Control group;

FIG. 10 depicts a graphical representation showing effect of chemotherapy on white blood cell (WBC) count of Study group and Control group;

FIG. 11 depicts a graphical representation showing effect of chemotherapy on platelet count of Study group and Control group;

FIG. 12 depicts a graphical representation showing effect of chemotherapy on Serum Bilirubin level of Study group and Control group;

FIG. 13 depicts a graphical representation showing effect of chemotherapy on SGPT level of Study group and Control group;

FIG. 14 depicts a graphical representation showing effect of chemotherapy on Serum Alkaline phosphatase level of Study group and Control group;

FIG. 15 depicts a graphical representation showing effect of chemotherapy on Serum Creatinine level of Study group and Control group;

FIG. 16 depicts a graphical representation showing effect of chemotherapy on CRP (C—reactive protein) level of Study group and Control group;

FIG. 17 depicts a graphical representation showing effect of chemotherapy on level of CA15.3 of Study group and Control group;

FIG. 18 depicts a graphical representation showing effect of chemotherapy on IL-1β (Interleukine-1β) level as fold change in Study group and Control group;

FIG. 19 depicts a graphical representation showing effect of chemotherapy on IL-6 (Interleukine-6) level as fold change in Study group and Control group;

FIG. 20 depicts a graphical representation showing effect of chemotherapy on IL-10 (Interleukine-10) level as fold change in Study group and Control group;

FIG. 21 depicts a graphical representation showing effect of chemotherapy on IL-8 (Interleukine-8) level as fold change in Study group and Control group;

FIG. 22 depicts a graphical representation showing effect of chemotherapy on SOD (Superoxide dismutase) activity as fold change in Study group and Control group;

FIG. 23 depicts a graphical representation showing effect of chemotherapy on catalase activity as fold change in Study group and Control group;

FIG. 24 depicts a graphical representation showing effect of chemotherapy on glutathione level as fold change in Study group and Control group;

FIG. 25A and FIG. 25B depict the results of clinical investigation for actual Karnofsky score and fold change respectively;

FIG. 26A depicts a graphical representation for Functional score and symptom score for both Study group and Control group;

FIG. 26B depicts a graphical representation for Global score and Breast score for both Study group and Control group;

FIG. 27 depicts a graphical representation showing effect of chemotherapy on anorexia, nausea, vomiting, constipation, dyspnea and dyspepsia of the patient described in case report 1 (Study group patient);

FIG. 28 depicts a graphical representation showing effect of chemotherapy on diarrhoea, taste alteration, mucositis, fatigue, and fever of the patient described in case report 1 (Study group patient);

FIG. 29 depicts a graphical representation showing effect of chemotherapy on IL-1β, IL-6, IL-8, and IL-10 levels in pg/ml units of the patient described in case report 1 (Study group patient);

FIG. 30 depicts a graphical representation showing effect of chemotherapy on SOD activity in U/ml, catalase activity in micro mole/min/ml, and glutathione level in micro mole/ml of the patient described in case report 1 (Study group patient);

FIG. 31 depicts a graphical representation showing effect of chemotherapy on Karnofsky score and weight of the patient described in case report 1 (Study group patient);

FIG. 32 depicts a graphical representation showing effect of chemotherapy on functional score, symptom score, global score, and breast score of the patient described in case report 1 (Study group patient);

FIG. 33 depicts a graphical representation showing effect of chemotherapy on anorexia, nausea, vomiting and diarrhoea of the patient described in case report 2 (Control group patient);

FIG. 34 depicts a graphical representation showing effect of chemotherapy on fatigue, dyspnea, fever, and mucositis of the patient described in case report 2 (Control group patient);

FIG. 35 depicts a graphical representation showing effect of chemotherapy on constipation, dyspepsia, and taste alteration of the patient described in case report 2 (Control group patient);

FIG. 36 depicts a graphical representation showing effect of chemotherapy on IL-1β, IL-6, IL-8, and IL-10 levels in pg/ml units of the patient described in case report 2 (Control group patient);

FIG. 37 depicts a graphical representation showing effect of chemotherapy on SOD activity in U/ml, catalase activity in micro mole/min/ml, and glutathione levels in micro mole/ml of the patient described in case report 2 (Control group patient);

FIG. 38 depicts a graphical representation showing effect of chemotherapy on Karnofsky score and weight of the patient described in case report 2 (Control group patient);

FIG. 39 depicts a graphical representation showing effect of chemotherapy on functional score, symptom score, global score, and breast score of the patient described in case report 2 (Control group patient);

FIG. 40 depicts a graphical representation showing comparison of reduction in adverse effects such as nausea, vomiting, constipation and stomatitis in group treated with present pharmaceutical kit (GR1), treated with combination of MKD, Ananta vati, Praval Pishti and PDG (GR2) and control group (GR3);

FIG. 41 depicts a graphical representation showing comparison of reduction in adverse effects such as fatigue, fever and skin discoloration in group treated with present pharmaceutical kit (GR1), treated with combination of MKD, Ananta vati, Praval Pishti and PDG (GR2) and control group (GR3);

FIG. 42A depicts a graphical representation showing comparison of quality of life (Karnofsky score, weight,) in group treated with present pharmaceutical kit (GR1), treated with combination of MKD, Ananta vati, Praval Pishti and PDG (GR2) and control group (GR3); and

FIG. 42B depicts a graphical representation showing comparison of quality of life (functional score, symptom score and global score) in group treated with present pharmaceutical kit (GR1), treated with combination of MKD, Ananta vati, Praval Pishti and PDG (GR2) and control group (GR3).

DETAILED DESCRIPTION

Embodiments, of the present disclosure, will now be described with reference to the accompanying drawing.

Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.

The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms “a,” “an,” and “the” may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms “comprises,” “comprising,” “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.

The incidence of breast cancer is increasing in women worldwide. Chemotherapy is used to reduce the primary tumour load as well as recurrence and metastasis. Although, chemotherapy is an unavoidable line of treatment for cancer, the adverse effects of chemotherapy frequently interfere with continuation of chemotherapy. The adverse effects are due to generation of oxidative stress, inability to control inflammation, reduction in immune response and functional impairment in tissues. These destructive effects result in impairment of quality of life of patients.

Therefore, the present disclosure provides a selected combination of pharmaceutical compositions, in the form of a kit.

The present disclosure deals with alleviating adverse side effects of chemotherapy, controlling oxidative stress, improving immune response and quality of life, if administered along with and continued after chemotherapy treatment.

In an aspect of the present disclosure, there is provided a pharmaceutical kit for alleviating immediate, intermediate, and late adverse effects of chemotherapy, reducing oxidative stress, improving immune status and quality of life.

The pharmaceutical kit comprising a first container containing Suvarna Bhasmadi Vati (SBD) in a solid dosage form, a second container containing Mouktikyukta Kamdudha Vati (MKD) in a solid dosage form, a third container containing Padmakadi Ghrut (PDG) in a thick, viscous form, and a fourth container containing Ananta vati in a solid dosage form.

A combination of SBD, MKD, PDG, and Ananta Vati in the kit is used for minimizing the adverse effects of chemotherapy and improving the quality of life. The adverse effects of chemotherapy are observed due to hampered function of gastrointestinal (GI) system, generation of oxidative stress, inability to control inflammation, reduction in immune response and functional impairment in tissues. These malfunctions are effectively corrected by the selected combination of pharmaceutical compositions, in the form of a kit, of the present disclosure.

The rationale for selecting the individual components of the kit and their compositions are as follows:

Suvarna Bhasmadi Vati (SBD) prepared in accordance with the present disclosure has been found to have the following effects in managing the adverse side effects of chemotherapy. SBD provides nourishment to body as well as to tissues which are hampered due to conventional systemic anti-cancer therapies. The anti-cancer therapies interfere with normal functions of GI system, produce inflammation in GI system, and interfere with the process of absorption of micro nutrients at cellular level. These malfunctions are effectively corrected by SBD. The quantities of Suvarna bhasma, Mouktik bhasma, and Guduchi sattva are carefully triturated. Although potency and duration of effectiveness of Suvarna bhasma is satisfactory, the addition of Mouktik bhasma and Guduchi sattva is needed for its easy absorption. Combining Suvarna bhasma with Mouktik bhasma and Guduchi sattva pacifies the aggressiveness of Suvarna Bhasma capacity on the digestive power as well as absorption at tissue level of the patient. Additionally Mouktik Bhasma has an antacid effect whereas Guduchi sattva is anti-pyretic and immunomodulator.

PDG in its unique combination, assists in minimizing the side effects of chemotherapy by rectifying the disorders of gastro-intestinal system, detoxifying blood, reducing inflammation and imparting hepato-protection. Cow's ghee in PDG holds the components of PDG together and improved their mode of action synergistically.

Ananta vati has mainly detoxifying effect in the blood. The active components of Ananta in Ananta Vati have an immediate effect in detoxifying the blood whereas the active components of Ananta bound in PDG provide sustained response. These active components are probably released slowly thus had long lasting immunomodulatory effect and improvement in anti-oxidant activity.

Thus, when the kit is administered in the form of combination, the SBD helps in improving immunomodulatory activity and rejuvenation effect. MKD has anti-emetic and carminative activity. Ananta Vati provides immediate detoxification of the blood and acts as a free oxidative radical scavenging agent while PDG smoothens GI tract and improves gross as well as micro level absorption, thus improving metabolism. All these four constituents of the pharmaceutical kit of present disclosure act synergistically in controlling ROS (Reactive oxygen species) generation, improving anti-inflammatory activity and immunomodulation, therefore reducing adverse side effects of chemotherapy and improving quality of life in cancer patients.

By way of example, the present kit envisaged in this disclosure is suitable as an adjuvant in the treatment for breast cancer in alleviating adverse side effects of chemotherapy and improving quality of life of the patients.

The SBD in the present pharmaceutical composition comprises Suvarna bhasma in an amount ranging from 2 wt % to 7 wt % of the total weight of the SBD, Mouktik bhasma in an amount ranging from 20 wt % to 35 wt % of the total weight of the SBD, Guduchi sattva in an amount ranging from 45 wt % to 60 wt % of the total weight of the SBD, and at least one excipient in an amount ranging from 5 wt % to 30 wt % of the total weight of the SBD.

Suvarna bhasma is known as incinerated gold and Mouktik bhasma is known incinerated pearl. The amount below 2 wt %, the Suvarna Bhasma will be sub-therapeutic and in quantities greater than 7 wt %, there will be an overload of the Bhasma which will be excreted. Similarly, the lower and upper weight percentages of the other ingredients i.e. Mouktik Bhasma and Guduchi Sattva have been triturated in this formulation keeping the above principle in mind. Ideally, after experimentation it is found that for optimum effect of SBD the composition should contain 4 wt % Suvarna Bhasma, 26 wt % Mouktik Bhasma, and 53 wt % Guduchi Sattva which are bound together with a natural gum such as gum acacia to the extent of 17 wt %.

The ingredients in powder form are blended together. The natural gum is added to the powder blend to form a dough along with purified water. Pellets are formed from this dough having average weight of 5 gm. The pellets are tray-dried typically at temperature in the range of 40° C. to 45° C. The dried pellets are granulated in a mixer grinder and the dry granules are taken for compression tableting. The average weight of the uncoated tablets is 240 mg±5%. The typical shelf life of the tablets is 3 years.

Guduchi is the common name for Tinospora. The Tinospora (Guduchi) plant is selected from Tinospora cordifolia and Tinospora sinensis. Particularly the stem of the plant is used for making the Sattva.

Tinospora cordifolia is also known as Guduchi of the family Menispermaceae. Tinospora cordifolia is indigenous to the tropical areas of India, Myanmar, and Sri Lanka. Tinospora cordifolia is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune.

Tinospora sinensis is also known as Malabar Gulbel or Gulvel of the family Menispermaceae. Tinospora sinensis is found in India, China, Sri Lanka, Nepal, Cambodia, Thailand, Vietnam, and Myanmar Tinospora sinensis is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune.

In an embodiment of the present disclosure, the excipient is binder. The binder is selected from the group consisting of gum acacia, guar gum, and xanthan gum.

The SBD is administered at a dose of 800 mg to 1000 mg per day by oral administration.

The MKD in the present pharmaceutical composition comprises Mouktik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shankha bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shouktik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Kapardik bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Praval bhasma in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Guduchi sattva in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, Shudhha Gairik in an amount ranging from 10 wt % to 14 wt % of the total weight of the MKD, and at least one excipient in an amount ranging from 10 wt % to 30 wt % of the total weight of the MKD.

The quantities below 10 wt % the Mouktik Bhasma will be sub-therapeutic and in quantities greater than 14 wt %, there will be an overload of the Bhasma which will be excreted.

Similarly, the lower and upper weight percentages of the other ingredients i.e. Praval Bhasma, Shankha Bhasma, Shouktik Bhasma, Kapardik Bhasma, Shudhha Gairik, and Guduchi Sattva have been triturated in this formulation keeping the above principle in mind. Ideally, after experimentation, it is found that for optimum effect of MKD the composition should contain equal amounts (12 wt % each) of Mouktik Bhasma, Praval Bhasma, Shankha Bhasma, Shouktik Bhasma, Kapardik Bhasma, Shudhha Gairik, and Guduchi Sattva as stated in classical texts, which are bound together with a natural gum such as gum acacia to the extent of 16 wt %. The ingredients in powder form are blended together. The natural gum is added to the powder blend to form a dough using purified water. Pellets are formed from this dough having average weight of 5 gm each. The pellets are tray-dried typically at temperature in the range of 40° C. to 45° C. The dried pellets are granulated in a mixer grinder and the dry granules are taken for compression tableting. The average weight of each uncoated tablet is 300 mg±5%. The typical shelf life of the tablets is 3 years.

The Tinospora (Guduchi) plant is selected from Tinospora cordifolia and Tinospora sinensis.

Tinospora cordifolia is also known as Guduchi of the family Menispermaceae. Tinospora cordifolia is indigenous to the tropical areas of India, Myanmar, and Sri Lanka. It is obtained from Bharatiya Sanskriti Darshan Trust, Pune.

Tinospora sinensis is also known as Malabar Gulbel or Gulvel of the family Menispermaceae. Tinospora sinensis is found in India, China, Sri Lanka, Nepal, Cambodia, Thailand, Vietnam, and Myanmar. It is obtained from Bharatiya Sanskriti Darshan Trust, Pune.

In one embodiment, the MKD comprises equal quantities of Mouktik bhasma, Shankha bhasma, Shouktik bhasma, Kapardik bhasma, Praval bhasma, Guduchi sattva and Shudhha Gairik and at least one edible binder, typically a natural gum, in an amount ranging from 10 wt % to 30 wt % of the total weight of the MKD.

In an embodiment of the present disclosure, the excipient is a binder, selected from the group consisting of gum acacia, guar gum, and xanthan gum.

The MKD is administered at a dose of 800 mg to 1200 mg per day by oral administration.

The PDG comprises:

i) extract of petals and stalks of Padmak, wherein the extract of Padmak is an extract obtained using at least one solvent selected from the group consisting of alcohol, water and a mixture thereof. Alternatively the extract is obtained by supercritical extraction;

ii) extract of whole Durva plant, wherein the extract of Durva is obtained using at least one solvent selected from the group consisting of alcohol, water and a mixture thereof. Alternatively the extract is obtained by supercritical extraction;

iii) decoction of roots of Ananta, wherein the decoction of Ananta is obtained using at least one solvent selected from the group consisting of alcohol, water, and a mixture thereof. Alternatively the extract is obtained by supercritical extraction; and

iv) Ghee obtained from cow's milk in an amount ranging from 90 wt % to 98 wt % of the total weight of the PDG.

The amount of the combined extract of petals and stalks of Padmak, whole Durva plant, and roots of Ananta is in the range of 2 wt % to 10 wt % of the total weight of PDG, and wherein the weight ratio of the extract of petals and stalks of Padmak to the extract of whole Durva plant to the decoction of roots of Ananta is 1:1:1.

Fresh juice of flower petals and stalks of Padmak, fresh juice of whole plant of Durva, and aqueous decoction of roots of Ananta are mixed with cow's ghee. The mixture is heated uniformly with stirring to evaporate the water completely. The complete removal of water is confirmed by the wick test. The active ingredients of the juices and decoction are dissolved or dispersed in the hot ghee. The hot mixture so obtained was filtered through muslin cloth to obtain PDG. The expiry of PDG is 2 years.

Nelumbo nucifera is commonly known as Padmak. Nelumbo nucifera is of the family Nymphaceae and the genus Nelumbo. Nelumbo nucifera is found in India, Sri Lanka, virtually all of Southeast Asia, New Guinea and northern and eastern Australia. Nelumbo nucifera is obtained from Bharatiya Sanskriti Darshan Trust, Wagholi, Pune.

Cynodon dactylon is commonly known as Durva of the family Poaceae. Cynodon dactylon is originated in the Middle East. It is also found in India, Bermuda, and North America. Cynodon dactylon is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune.

Ananta is Decalepis hamiltonni. Decalepis hamiltonii is commonly used as Ananta. Decalepis hamiltonii is of the family Apocynaceae. It is found in South India. Decalepis hamiltonii is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune. Ananta is roots of Decalepis hamiltonii (Swallow roots) or Hemidesmus indicus or Cryptolepis buchnani or Ichnocarpus frutescens. In an embodiment, Ananta is Decalepis hamiltonii (Swallow roots). Decalepis hamiltonii (Swallow roots) is used due to commercial availability, however, it is asserted that Hemidesmus indicus or Cryptolepis buchnani or Ichnocarpus frutescens will equally be effective, alone or in combination with each other.

Cow Ghee is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune. PDG is administered at a dose of 8 gm to 12 gm per day by oral administration.

In an embodiment of the present disclosure, the PDG is prepared in the form of a thick viscous liquid.

The Ananta vati comprises powder obtained from dried roots of Ananta (Decalepis hamiltonii) in an amount ranging from 75 wt % to 92 wt % of the total weight of the Ananta vati, wherein the powder has a particle size in the range of 150 to 180 microns, and at least one excipient in an amount ranging from 8 wt % to 25 wt % of the total weight of the Ananta vati.

Ananta powder is mixed with natural gum to form a dough along with purified water. Pellets are formed from this dough having average of 5 gm. These pellets are tray dried typically at temperature in the range of 40-45° C. The dried pellets are granulated in a mixer grinder and the dry granules are taken for compression tableting. The average weight of the uncoated tablets is 300 mg±5%. The typical shelf life of these tablets is 3 years.

Ananta is Decalepis hamiltonni. Decalepis hamiltonni is obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune. Other Ananta species such as Hemidesmus indicus, Cryptolepis buchnani, Ichnocarpus frutescens, and the like also can be used in the pharmaceutical kit of the present disclosure.

In an embodiment of the present disclosure, the excipient is gum acacia.

The Ananta vati is administered at a dose of 1.8 mg to 2.2 gm per day by oral route.

The compositions of SBD, MKD, and Ananta vati are prepared in the form of a solid unit dosage form selected from the group consisting of tablet, pill, and capsule.

The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.

The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.

EXPERIMENTAL DETAIL
Example 1

A pharmaceutical kit was prepared in accordance with the present disclosure.

The components of the pharmaceutical kit containing oral medicines are given in Table-1.

TABLE 1

Components of the pharmaceutical kit containing oral medicines

Sr.

Quantity

No.
Medicine
per dose
Time

1
SBD
395 mg
Morning after breakfast (8.00am)-

(2 tablets)
Evening after snacks (5.00pm)

2
MKD
500 mg
Morning after breakfast (8.00am)-

(2 tablets)
Evening after snacks (5.00pm)

3
PDG
5 gm
Before Lunch and Dinner

(1 tsp)

4
Ananta Vati
1 gm
After Lunch and Dinner

(4 tablets)

Experiment 1: Composition of SBD in Accordance with the Present Disclosure

Result:

SBD was prepared using the following ingredients as given in Table-2.

TABLE 2

Composition of SBD

Quantity
Quantity
Quantity

for 5 kg
for 5 kg
for 5 kg

Sr.

Latin name/
batch-
batch-
batch-

No.
Contents
English Name
Batch 1
Batch 2
Batch 3

1
Suvarna Bhasma
Incinerated Gold
210.97 g
110 g
350 g

2
Mouktik Bhasma
Incinerated Pearl
1318.56 g
1700 g
1000 g

3
Aqueous extract
Starch of Tinospora
2637.1 g
2940 g
2250 g

of Tinospora

cordifolia/sinensis

cordifolia/sinensis

4
Gum Acacia

833.33 g
250 g
1400 g

powder

Process for Preparing SBD:

Step 1: Preparation of Suvarna Bhasma

Initially, 300 gm of Suvarna foils were amalgamated with 2500 gm of metallic mercury and 2500 gm of sulphur powder having particle size 150 microns and then incinerated 18 times each at 650° C. for 6 hours to get incinerated Suvarna. For stabilization, the incinerated Suvarna was triturated for 6 hours with 200 ml fresh juice of the leaves of Ocimum sanctum (Tulsi) and further incinerated at 600° C. for 5 hours. This process of incineration in Tulsi juice was repeated 25 times to obtain Suvarna Bhasma having particle size in the range of 20-500 nm (average particle size 350 nm). The particle size of the so obtained Suvarna Bhasma were analysed by particle size analyser (90 plus from Brookhaven Instruments, USA).

Tulsi—Ocimum sanctum is also known as holy basil of the family Lamiaceae. Ocimum sanctum was obtained from Bharatiya Sanskriti Darshan Trust (BSDT), Wagholi, Pune.

Specification of Suvarna bhasma:

Description: Brown coloured, very fine free flowing powder

Loss on Drying—NMT 0.5% w/w

Loss on Ignition—NMT 1% w/w

Acid insoluble ash—90 to 98% w/w

Assay as Au—NLT 85% w/w

Step 2: Preparation of Mountie Bhasma

8 Kg Mountie (pearl) was boiled in 32 L of butter milk having curd to water ratio of 1:2 w/v and pH of 3, to obtain purified Mouktik. The so obtained purified Mouktik was powdered and triturated with 4 L of rose water to obtain triturated powder. The triturated powder was then incinerated using cow-dung cakes at 700° C. to obtain Mouktik Bhasma (incinerated pearl).

Specification of Mouktik Bhasma:

Description: Greyish white coloured, very fine powder

Loss on Drying—NMT 0.5% w/w

Acid insoluble ash—NMT 2% w/w

Calcium assay—38 to 40% w/w

pH—10 to 11

Step 3: Extraction of starch from Tinospora cordifolia

50 Kg of fresh stems of Tinospora cordifolia were chopped into small pieces. These pieces were crushed and then soaked for 12 hours in 4 times (w/v) of potable water (200 L) in a stainless steel vessel. The mixture was macerated in water thoroughly and filtered slowly to obtain solution containing aqueous extract of Tinospora cordifolia. The solution thus obtained was kept aside for 12 hours to obtain supernatant and smooth starchy sediment of Tinospora cordifolia. The supernatant was carefully separated to obtain smooth starchy sediment. The smooth starchy sediment of Tinospora cordifolia was evaporated in an oven at 45° C. to obtain Guduchi Sattva in the form of dry starch.

Specification of Starch Extract of Tinospora cordifolia:

Description: Greyish white coloured very fine free flowing starchy powder

Loss on Drying—NMT 5% w/w

Acid insoluble ash—NMT 1% w/w

Gelation temperature—60 to 75° C.

Step 4: Preparation of SBD

In a mixer, Suvarna bhasma, Mauktik bhasma, Guduchi Sattva (starch from Tinospora cordifolia), and gum acacia were mixed in a proportion given in Table 2. To this mixture, sufficient amount of water was added to obtain a dough. The dough was further pelletized to obtain pellets. The pellets were dried in oven at 45° C. to obtain dried pellets. The dried pellets were grinded to obtain granules having powder to granule ratio of 30:70. The mixture of granules and powder was compressed in tablet punching machine to obtain compressed tablet of weight 237±5 mg.

Specifications of SBD:

Appearance: Grey colour, round

Shape: Biconvex tablets

Weight variation: 0.2210 to 0.2300

Average weight: 0.2300 to 0.2500

Hardness: 1-2 Kg/cm²

Friability: NMT 1% w/w

Disintegration Time: NMT 30 min

Diameter: 7 to 7.5 mm

Width: 3.3 to 4.6 mm

Acute toxicity: LD 50>2000 mg/kg

Experiment 2: Composition of MKD in Accordance with the Present Disclosure

Result:

MKD was prepared using the following ingredients as given in Table-3.

TABLE 3

Composition of MKD

Quantity
Quantity
Quantity

for 30 kg
for 30 kg
for 30 kg

Sr.

Latin name/
batch-
batch-
batch-

No.
Contents
English Name
Batch 1
Batch 2
Batch 3

1
Mouktik Bhasma
Incinerated Pearl
3572 g
3500
4000

2
Shankha Bhasma
Incinerated Conch
3572 g
3000
3800

3
Shouktik Bhasma
Incinerated Pearl Shell
3572 g
3000
3800

4
Kapardik Bhasma
Incinerated Cowrie
3572 g
3000
3800

5
Praval Bhasma
Incinerated Coral
3572 g
3500
3800

6
An aqueous extract
Starch of Tinospora
3572 g
3500
4000

of Tinospora

cordifolia/sinensis

cordifolia/sinensis

7
Shudhha Gairik
Red ochre roasted in
3572 g
3000
3800

cow ghee

8
Gum Acacia

5000 g
7500
3000

powder

Process for Preparing MKD:

Mouktik bhasma, Shankha bhasma, Shouktik bhasma, Kapardik bhasma, Praval bhasma (all these five bhasma are prepared using textual methods), starch of Tinospora cordifolia/sinensis, Shudhha Gairik and gum acacia powder were mixed in a proportion given in Table 3. To this mixture, sufficient amount of potable water was added to obtain a dough. The dough was further pelletized to obtain pellets. The pellets were dried in oven at 45° C. to obtain dried pellets. The dried pellets were grinded to obtain granules having powder to granule ratio of 30:70. The mixture of granules and powder was compressed in tablet punching machine to obtain compressed tablet of weight 300±5 mg.

Specification of Shankha Bhasma: