WO2017174109A1

WO2017174109A1 - Herbal product for treatment of diabetes mellitus

Info

Publication number: WO2017174109A1
Application number: PCT/EP2016/057335
Authority: WO
Inventors: Abdulmajeed Aziz ALZANDANI; Mohammed Abdulmajeed Aziz ALZANDANI
Original assignee: Alzandani Abdulmajeed Aziz; Alzandani Mohammed Abdulmajeed Aziz
Priority date: 2016-04-04
Filing date: 2016-04-04
Publication date: 2017-10-12
Also published as: TR201802107T1

Abstract

The present invention relates to a herbal product obtained from a distillate of a Costus root extract for use in treatment of diabetes mellitus. More particularly, the present invention pertains to a herbal product as mentioned above for use in stimulating HbA1c, C-peptide, insulin and blood glucose levels in a diabetic patient.

Description

HERBAL PRODUCT FOR TREATMENT OF DIABETES MELLITUS

Technical Field of the Invention

The present invention relates to an herbal product of Costus root useful for the treatment of diabetes mellitus. The invention particularly relates to a novel herbal product derived from Costus roots stimulating the level of glucose, HbAlc, C-peptide and insulin in blood plasma.

Background of the Invention

Diabetes mellitus is a disease caused by either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced. More particularly, Type 1 diabetes results from failure of the pancreas to produce enough insulin (insulin dependent diabetes), while Type 2 is characterized by insulin resistance, a condition in which cells fail to respond to insulin properly (non-insulin dependent diabetes).

There are various peptides and hormones playing an important role in development of diabetes and these can be easily measured qualitatively and quantitatively with conventional test procedures usually using a blood sample from the patient.

The level of insulin in blood plasma, for instance varies largely in diabetic patients. A low level of insulin can be caused by Type 1 diabetes where the pancreas fails to produce enough insulin. Excess levels of insulin (hyperinsulinemia), on the other hand, is caused by reduced response to insulin, namely that the beta cells of the pancreas secrete increasing amounts of insulin in response to the continued high blood glucose levels.

HbAlc (glycated hemoglobin) is another factor in diabetes mellitus, and higher amounts thereof indicates poorer control of blood glucose levels, and said higher amounts can be associated with cardiovascular disease, nephropathy, neuropathy and retinopathy. When blood glucose levels are high, glucose molecules attach to the hemoglobin in red blood cells. The longer hyperglycemia occurs in blood, the more glucose binds to hemoglobin in the red blood cells and the higher the glycated hemoglobin.

C-peptide, on the other hand, is an important polypeptide that connects A-chain and B- chain of insulin, and it is removed later on after constitution of the insulin molecule. A very low C-peptide confirms Type 1 diabetes and insulin dependence, and is associated with high glucose variability, hypoglycaemia and increased complications. Higher levels of C-peptide together with the presence of a gastrinoma suggest that organs besides the stomach may harbor neoplasms.

There are also various parameters associated with glucose in blood which can be indicative of diabetes mellitus. Among these, FBS (Fasting Blood Sugar), PPBS (Postprandial Blood Sugar) and RBS (Random Blood Sugar) are important. Measuring FBS, PPBS and RBS enable investigation of whether a person may have diabetes, or of whether persons having diabetes are successfully controlling their blood sugar.

Conventional therapies with insulin and drugs have several complications, burdensome and expensive. Furthermore, conventional therapies suggest acute treatment of symptoms and are used along lifespan of the patient. It is therefore preferable to use herbal therapies as a replacement or adjuvant therapy in diabetics. Herbal therapies are also advantageous because they can be used as a food supplement in frame of a diet program, or as an adjuvant therapy without affecting the actual therapy along with pharmaceutical medicaments. WO 2011/039574 Al discloses a herbal composition of the foregoing type comprising an extract of Costus root and therapeutical effects thereof including, inter alia, diabetes. This document, however scrutinizes in general the advantageous effects of the Costus root on HIV. Therefore, there is a continuous need to develop herbal products specifically designed for the treatment of diabetes mellitus in a more effective way. It is also needed in the prior art to provide herbal products which stimulate the insulin, glucose, HbAlc and C-peptide levels in the blood. Accordingly, an object of the present invention is to provide a novel herbal product which is effective for the treatment of diabetes mellitus.

Another object of the present invention to provide a food supplement acting as an adjuvant and supporting the conventional therapies to control diabetes mellitus.

A further object of the present invention is providing a novel herbal product which successfully stimulates the insulin, glucose, HbAlc and C-peptide levels in a diabetic patient.

Still a further object of the present invention is providing a method for producing an herbal product which is brought to a more effective form.

These and other objectives of the instant invention have been achieved with the novel herbal product according to claim 1.

Brief Description of the Figures

Figure 1 is a diagram showing HbAlc and C-peptide levels in a 34 year-old male receiving the herbal product according to the present invention.

Figure 2 is a diagram showing HbAlc and C-peptide levels in a 6 year-old pediatric patient receiving the herbal product according to the present invention.

Figure 3 is a diagram showing HbAlc and C-peptide levels in a 50 year-old female receiving the herbal product according to the present invention.

Detailed Description of Invention

The present invention relates to a novel herbal product of Costus root for the treatment of diabetes mellitus. Costus root is traditionally known be effective for treatment of various infections, as well as asthma, cough and intestinal diseases. It is also cited in the Chinese traditional medicine that herb is often used to treat anicteric hepatitis and chronic persistent hepatitis, cholecystitis, infantile enteritis, bacillary dysentery, colic, flatulence, peptic ulcer, Diarrhea, Predominant Irritable Bowel Syndrome (IBS-D), and dysmenorrhea.

The major components found in Costus roots can be listed as follows: Hepatadecatetraene, 12-methoxy-dihydrocostunolide, 22-dihydrostigmasterol, 3- isopropropylpentanoic-acid, 3-methylbutyric-acid, 4-ethyloctanoic-acid, 7-octenoic-acid, Acetic-acid, Alkaloids, Alpha-humulene, Alpha-phellandrene, Alpha-costene, Alpha- amorphenic-acid, Alpha-amyrin-stearate, Alpha-ionone, Aplotaxene Beta-sitosterol, Beta- selinine, Beta-costene, Beta-ionone, Beta-elemene, Beta-amyrin-stearate, Betulin, Camphene, Caryophyllene, Caryophyllene-oxide, Cedrene, Cedrol, Cis-dihydroionone, Costic-acid, Costol, Constunolide Costus-acid, Costus-lactone, Dehydrocostus-lactone, Dihydrodehydrocostus-lactone, Dihydroaplotacene, Dihydrocostunolide, Dihydrocostus- lactone, EO, Friedelin, Guaia-3,9,ll-triene-12-acid, Heptanoic-acid, Hexanoic-acid, lnulin, Iszaluzanin, Kushtin, Lactones, Linalool, Leupeol, Myrcene, Naphthaline, Octanoic-acid, Oleic-acid, P-cymene, Palmitic-acid, Pentadec-l-ene, Phellandrene, Resinoids, Saussurine, Stigmasterol, Tannin, Taraxasterol, Dihydrocostuslactone, dihydrocostunolide and alpotaxene.

The Costus root used in the context of the present invention is preferably of the type Aucklandia-Costus (Saussurea lappa) within the genus of Saussurea. In Siddha medicine, it is known as Kostum. The pharmaceutical name is Radix Auklandiae Lappae. Auklandia costus root comes from a perennial plant [Saussurea Lappa-Costus], that grows to about 2m in height and is native to Northern India, South West China and Pakistan. It has irregular, triangular-shaped leaves and dark blue or black florets, with brownish fruit.

Costus root, just as the other conventional herbal products, is generally processed with simply an extraction procedure whereby the beneficial material of the plant is extracted through a liquid medium possibly at an elevated temperature, and this liquid medium as such or its dry material is used by the patient. The inventors, however noted that lighter fraction of the costus content is mostly lost during the extraction step at an elevated temperature, and surprisingly found that the said lighter fraction would in fact be useful for the treatment of diabetes mellitus, and more particularly for stimulating insulin, glucose, HbAlc and C-peptide levels in a diabetic patient. Therefore, the present invention is directed to a novel method for producing a herbal product derived from Costus root including lighter fraction of the plant. The present invention pertains also to the novel herbal product obtainable with this method.

Accordingly, the method of the current invention comprises; - treating Costus root with an aqueous medium and extracting content of the plant material,

distillation of the extract, and

obtaining the distillate in liquid form. As noted above, the distillate as such as is a novel herbal product and therefore the invention is also directed to the distillate obtainable by the foregoing method.

In the context of the present invention, distillation is carried out once. However, even lighter and poorer fractions can be obtained by further distillations. The distillation refers to an evaporation which can be carried out at a temperature around the reflux temperature of the extraction liqueur. The temperature can be below 100°C, more preferably below 95°C, and most preferably at a temperature ranging from 70°C to 90°C. The distillation period is preferably from 1 h to 8 h, and more particularly between 1 h to 3 h.

The ratio of plant material to the aqueous medium can be ranging from 1:20 to 1:5 (weight/volume). Preferably, this ratio is around 1:10 (w/v).

The Costus root plant material is preferably dried before the extraction step and is sliced into pieces for effectuating the mass transfer between the plant material and the extraction medium. The distillate obtained in the method of the present invention may be used directly as such in liquid form, or it can be dried to give a solid or semi-solid preparation. Therefore, the herbal product of the present invention can be used orally in various dosage forms such as solution, suspension, tablet, or capsule with or without pharmaceutically acceptable excipients. Alternatively, it can be used via parenteral, rectal or vaginal routes and therefore the herbal product of the present invention can be conveniently formulated as an injection or suppository.

The dosage of the herbal compositions of the invention will vary depending on factors such as the severity of the condition being treated, age, physical condition and body weight of the patient, diet and the like. However, an advantage of the invention is that the actual dosage is not critical since the compositions of the invention are holistic in nature and represent dietary supplements in their own right. Overdosing is accordingly not a problem. An individual patient with a particular body weight and life style may readily determine a proper dosage by starting out with a general dosage.

However, in the preferred embodiments, the present invention relates to oral dosage regimen of the herbal product according to the present invention. It is noted that unit doses comprising the distilled fraction of the plant extract ranging from 5 ml to 10 ml can be effective for controlling diabetes and particularly for stimulating insulin, glucose, HbAlc and C-peptide levels in a diabetic patient. The preferred dosage regime is twice in a day before the meals. It is noted that the following doses would be useful depending on the weight of the patient.

5 ml : <60 kg,

- 7.5 ml : 60-100 kg

- 10 ml : > 100 kg

Toxicity studies have been carried out as explained in WO 2011/039574 Al which is incorporated herein as a reference.

In a further aspect of the present invention, the herbal product disclosed herein can be used as a therapy, adjuvant therapy or merely as a food supplement as part of a diet programme of the patient. It has been seen in the toxicity assays that the herbal product of the present invention is safe and does not constitute overdosing problems or interaction/incompatibility with other medications. Therefore, it can readily be used as a first line of therapy, and/or as an adjuvant that can be useful for increasing the effect of conventional therapies.

Example 1

Preparation of the herbal product

Roots of Aucklandia-(Costus Root) were air dried in direct sunlight until the insides of the roots became black. The dried roots were then sliced before use. The sliced, dried, roots were then ground to a powder. The powdered plant material (1 kg) was placed in 10 L of water contained in a pot equipped with a water jacketed distillation line whereby water as a coolant is continuously circulated around the said distillation line. The extraction liqueur formed with the plant material and water is heated until 90°C with a temperature controlled heater, and kept at this temperature for about 3 hours. The vaporized liqueur passing through the distillation line is condensed and collected in a flask in liquid form. The liquid obtained with the foregoing procedure constitutes lighter fraction of the plant material in Costus roots.

Example 2

Patient Studies

Patient No: 1

A 34 year-old male who has not been received previously a diabetic therapy was prescribed for using 10 ml of the distillate before meals in the mornings and evenings. The patient used the herbal product starting from 24.11.2012 without additional medicaments and a specific diet programme. The blood samples of the patient have been analysed by Modern International Lab, Yemen. It is noted that HbAlc, C-peptide and insulin levels have been stimulated but a dramatic change is also noted in FBS (Fasting Blood Sugar) values as shown in Table 1. A graphical representation of the HbAlc and C- peptide levels is given in Fig. 1. Table 1 (Patient No: 1)

Patient No: 2 A 6 year-old paediatric patient diagnosed with Type-1 diabetes mellitus and not having been received previously a diabetic therapy has been prescribed for using 5 ml of the distillate before meals in the mornings and evenings. The patient used the herbal product starting from 20.01.2013 without additional medicaments and a specific diet programme. The blood samples of the patient have been analysed by Aulaqi Specialized Med. Lab (Dr. Saleh M. Aulaqi - Consultant Pathologist, FRCP Canada). It is noted that HbAlc, C-peptide and insulin levels have been stimulated through the normal levels as shown in Table 2. A graphical illustration of HbAlc and C-peptide levels is given in Fig. 2.

Table 2 (Patient No: 2)

Patient No: 3

A 50 year-old female patient who was diagnosed with Type-2 diabetes mellitus and not having been received previously a diabetic therapy has been prescribed for using 10 ml of the distillate before meals in the mornings and evenings. The patient used the herbal product starting from 09.01.2013 without additional medicaments and a specific diet programme. The blood samples of the patient have been analysed by Aulaqi Specialized Med. Lab (Dr. Saleh M. Aulaqi - Consultant Pathologist, FRCP Canada). It is noted that HbAlc, C-peptide and insulin levels have been stimulated through the normal levels as shown in Table 3, a graphical representation of which is given also in Fig. 3:

Table 3

Test 09.01.2013 19.02.2013 06.05.2013 Reference Values

HbAlc 11.0 9.0 7.8 < 5.5 %

C-peptide 0.4 2.2 - 1.1 - 3.6 ng/ml

Insulin 79 9.4 - 3 - 17 uU/mL

Claims

A herbal product comprising a distillate of a Costus root extract for use in treatment of diabetes mellitus.

A herbal product according to claim 1 for use in stimulating HbAlc, C-peptide and insulin levels in a diabetic patient.

A herbal product according to claim 1 wherein the plant Costus is an Auclandia- Costus.

A herbal product according to claim 1 wherein the product is for treatment of a diabetic patient with a dosage regime of twice a day.

A herbal product according to claim 1 wherein the distillate is in a pharmaceutical dosage form selected from solution, suspension, tablet, capsule, suppository and a parenteral injection form.

A method for producing a herbal product comprising the steps of:

treating Costus root with an aqueous medium and extracting content of the plant material,

distillation of the extract, and

obtaining the distillate in liquid form.

A method according to claim 6 wherein the plant Costus is an Auclandia-Costus.

A method according to claim 6 wherein temperature of distillation is below 100°C.

A method according to claim 8 wherein temperature of distillation is between 70°C to 90°C.

A method according to claim 6 wherein ratio of the costus plant material to the aqueous medium ranges from 1:20 to 1:5 (w/v).

11. A method according to claim 10 wherein ratio of the costus plant material to the aqueous medium is about 1: 10 (w/v).

12. A method according to claim 6 wherein duration of the distillation is from 1 hour to 8 hours.

13. A method according to claim 10 wherein the method further comprises preparation of unit doses comprising 5 ml to 10 ml of the distillate.

14. A herbal product obtainable by the process of claim 6.

15. The product of claim 14 which is a food supplement.