PHARMACEUTICAL COMPOSITION BASED ON PLANT EXTRACTS FOR THE TREATMENT OF FIBROMYALGIA, RHEUMATOID ARTHRITIS, LUPUS AND OTHER AUTOIMMUNE DISEASES

Abstract

The present invention relates to compositions and pharmaceutical forms for the treatment of fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus and autoimmune diseases associated with pain and inflammation of the muscles and joints with natural active ingredients in the form of lyophilized powders of aqueous extracts of Dandelion (Taraxacum officinale), Watermelon (Citrullus lanatus), Mapuey or white yam, (Dioscorea trifid), Licorice (Glycyrrhiza glabra), tomato (Solanum lycopersicum) and bay leaves (Laurus nobilis), as well as procedures for obtaining and preparing associated with the development of the different compositions and pharmaceutical forms.

Claims

1. A pharmaceutical composition for the treatment of fibromyalgia, arthritis rheumatoid, systemic lupus erythematosus and associated autoimmune diseases with pain and inflammation of the muscles and joints that have as natural active ingredients in the form of lyophilized powders of aqueous extracts, the composition comprising: dandelion (Taraxacum officinale), watermelon (Citrullus lanatus), mapuey or white yam, (Dioscorea trifid), licorice (Glycyrrhiza glabra), tomato (Solanum lycopersicum), bay leaves (Laurus nobilis), and preservatives.

2. The composition of claim 1, wherein the composition comprises: TABLE-US-00007 dandelion lyophilized extract 10%-50% watermelon extract 10%-30% mapuey extract  4%-15% licorice extract 4%-7% tomato extract 1%-3% laurel extract 1%-5% sodium benzoate extract 0.25% potassium sorbate extract 0.25% treated water (optionally)  15%-19.5%.

3. The composition of claim 1, wherein the composition is a hard gelatin capsule for oral administration and comprises: TABLE-US-00008 dandelion 40%  watermelon 27.5%   mapuey 15%  licorice 7% tomato 5% bay 5% sodium benzoate 0.25%   potassium sorbate 0.25%. 

4. The composition of claim 1, wherein the composition is a tea or infusion formulated in a bag or sack of porous paper, silk, or nylon to be dissolved in hot water and comprises: TABLE-US-00009 dandelion 40%  watermelon 39.5%   mapuey 8% licorice 7% tomato 3% bay 2% sodium benzoate 0.25%   potassium sorbate 0.25%. 

5. The composition of claim 1, wherein the composition is a drinkable ampoule and comprises: TABLE-US-00010 properly treated water 19.5%   dandelion lyophilized extract 30%  watermelon extract 30%  mapuey extract 8% licorice extract 7% tomato extract 3% laurel extract 2% sodium benzoate 0.25%   potassium sorbate 0.25%. 

6. The composition of claim 1, wherein the composition is an intramuscular injectable solution and comprises: TABLE-US-00011 treated water 18.01%    dandelion extract 30%  watermelon extract 30%  mapuey extract 8% licoriceextract 7% tomato extract 3% laurel extract 2% lidocaine 1.8%.sup.  benzoic acid 0.17%   ascorbic acid 0.02%. 

7. (canceled)

8. The method the treatment of fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus and autoimmune diseases associated with pain and inflammation of the muscles and joints, the method comprising the step of administering to a person in need of the composition according to claim 3.

9-11. (canceled)

Description

DETAILED DESCRIPTION OF THE INVENTION

[0024] The qualitative and quantitative composition by weight of the active ingredients, solvents and preservatives that are proposed in this formulation as well as their function within the composition is as follows:

TABLE-US-00001 Freeze-dried extract of Dandelion 10%-50% Active Ingredient Watermelon Extract 10%-30% Active Ingredient Mapuey Extract  4%-15% Active Ingredient Liquorice Extract 4%-7% Active Ingredient Tomato Extract 1%-3% Active Ingredient Laurel Extract 1%-5% Active Ingredient Sodium Benzoate Extract 0.25% Perseverant Potassium Sorbate Extract 0.25% Perseverant Treated Water (optionally) .sup. 15%-19.5% Solvent

Procedure for Making Capsules:

[0025] The procedure developed for the manufacture of capsules consists of several stages that first go through a classification and selection phase, then proceed to mix with heat between 30 and 40° C., then lead to aqueous extraction of the active ingredients at temperatures of 90 to 96° C. with stirring every five minutes, later this extract is filtered and add the persevantes salts and proceed immediately to the spraying by dried in a Spray Dryer ADL 311, then the powder thus obtained is taken to the encapsulation process in hard gelatin capsules.

[0026] The procedure for preparing these capsules includes several stages: [0027] 1. In the first stage of the process, the different raw materials are prepared, which entails the inspection, classification, and approval of the raw material to be used in the production of the final product, which will reach a final product in powder form which is introduced into hard gelatin capsules. [0028] 2. After the raw materials have been approved in the receiving area of raw materials, they go to the pre-production area where they are prepared for entry into the production area, it is in this area where they are removed the shell to those raw materials that require it, as well as the seeds, they are cleaned and rinsed with treated water coming from the plant of treatment. [0029] 3. As the raw materials leave this area, they enter the production area where enter a stainless-steel mixer with temperature control, which is fed with steam from a pyro-tubular boiler, which allows achieving the temperature rise in it. In this mixer we add all the raw materials of the formula minus the preservatives, because these must be added in the final stage of the process at a temperature of 30° C. to 40° C. to prevent its degradation by temperature and then damage the product through weather. [0030] In this mixer the different raw materials all mixed inside the same, they are subjected to a temperature of 96° C. (205° F.), followed by periods of agitation every 5 minutes, this with the aim that at that temperature the water can absorb the properties and nutrients of each of the raw materials present in the mixer, this will allow us to obtain a well charged liquid, rich of all the properties from the herbs, fruits and raw materials that were subjected in this part of the production process. [0031] 4. The resulting liquid that comes out of the mixer now goes to another piece of equipment called pressure filter, it is in this equipment where even the smallest particle is separated solid that may be mixed with the liquid extract, the objective in this part of the process is to obtain a liquid free of solid particles. In this stage We will take the opportunity to add the Preservatives. [0032] 5. The already filtered liquid is passed to a pulverizing equipment or dryer by spraying of the Spray Dryer ADL 311 type, at this stage of the process what is achieve is that the liquid from the pressure filter turns into dust. The feed of the concentrated and filtered liquid is fed by means of a pump peristaltic with silicone hose, this spray equipment has a temperature system, spray system at the tip of the nozzle outlet, blower, heater, suction filter and exhaust filter, through the which performs the drying and subsequent spraying of the liquid, managing to convert it into dust. [0033] 6. Dust obtained from Spray equipment now passes through to a Machine Encapsulator NJP 1200D, which is an automatic machine that allows encapsulate the powder product in Gelatin Capsules, which can be Capsules of #0 Gelatin, for example in Red/Black #0 hard gelatin capsules, from the company ACG Associated Capsules Pvt Ltd. [0034] 7. Once the product is encapsulated, these capsules are now going to pass through a piece of equipment called SP-G100 Capsule Packing Machine, the goal to be achieved in this equipment is to place the capsules in the final packaging, which will serve as vehicle to deliver the product to the final consumer.
The capsules thus obtained according to the process described have a stability 2-year storage environment.

Example 1

[0035] With the capsules obtained according to example 1, they were subjected to treatment of patients diagnosed with fibromyalgia, rheumatoid arthritis and lupus erythematosus systemic and autoimmune diseases associated with pain and inflammation of muscles and joints for a period of one month with a dosage of two capsules a day with a composition of ingredients of:

TABLE-US-00002 Lion Teeth .sup. 40% Watermelon 27.5% Mapuey .sup. 15% Licorice   7% Tomato   5% Bay   5% Sodium Benzoate 0.25% Potassium sorbate 0.25%

Procedure for Making Tea Bags:

[0036] The homogeneous powder obtained according to steps 1 to 5 described in the procedure for obtaining the capsules is now packed in bags or sacks of porous paper, silk or nylon, similar to those used in tea bags or similar from which an infusion is prepared with hot water useful in the treatment of fibromyalgia and autoimmune diseases.

[0037] The bags thus obtained according to the described process have an ambient stability 2-year storage.

Example 2

[0038] Patients diagnosed with fibromyalgia, arthritis rheumatoid and systemic lupus erythematosus and associated autoimmune diseases with pain and swelling of the muscles and joints for a period of a month with a dosage of four to six cups of tea per day, with a composition of ingredients per bag:

TABLE-US-00003 Lion Teeth 50%  Watermelon 29.5%   Mapuey 8% Licorice 7% Tomato 3% Bay 2% Sodium Benzoate 0.25%   Potassium sorbate 0.25%  

Procedure for the Preparation of a Bag of Drinkable Ampoules:

[0039] The procedure for the preparation of drinkable ampoules consists of the following Steps: [0040] 1. In the first stage of the process, the different raw materials are received in the plant, which will go through a process of inspection, classification, and approval to be used in the production of our final product, which will be ampoules drinkable. [0041] 2. After the raw materials have been approved in the receiving area of raw materials, they go to the pre-production area where they are prepared for entry into the production area, it is in this area where they are removed the shell to those raw materials that require it, as well as the seeds, they are cleaned and rinsed with treated water coming from the plant of treatment. [0042] 3. As the raw materials leave this area, they enter the production area where the first piece of equipment or unit operation they enter is a steel mixer stainless steel with temperature control, which is fed with steam, which allows to achieve the temperature increase in it. in this mixer we add all the raw materials of our formula except the Preservatives, because these must be added at a temperature of 30° C. to 40° C. to avoid its degradation due to high temperatures and that later the product cannot be supplied expected effect on the final product. [0043] 4. In this mixer the different raw materials all mixed inside the same, they are subjected to a temperature of 96° C. (205° F.), followed by periods of agitation every 5 minutes, this with the aim that at that temperature the water can absorb the properties and nutrients of each of the raw materials present in the mixer, this will allow us to obtain a well charged liquid, rich of all the properties from the herbs, fruits and raw materials that were subjected in this part of our production process. [0044] 5. The resulting solution that comes out of the mixer now goes to another piece of equipment called pressure filter, it is in this equipment that even the smallest particle is separated solid that can be mixed with our solution, the objective in this part of the process is to obtain a solution free of solid particles. In this stage we will take the opportunity to add those pending products that we did not add in the previous stage due to high temperatures, these are Sodium Benzoate and Potassium Sorbate. [0045] 6. The container chosen to store the final product is the container: Ampoules Specials For Drinkable Solutions. [0046] 7. These containers are subjected to an automatic washing process in a machine that provides pressurized water jet, this water is totally purified. [0047] 8. Once these containers leave the washing process, they enter a machine sterilization or dryer that will be responsible for sterilizing and drying the containers by the action of high temperatures. [0048] 9. Upon leaving the sterilization machine or dryer, these containers enter a SCT Pharma oven, where the depyrogenation process will be carried out, which is nothing more than that process that will allow us the total or almost total reduction of bacterial endotoxins (pyrogens), in other words what we are looking for is to obtain ampoules free of all microorganisms and undesirable pathogenic substances, this we achieve this through processes that use high temperatures, such as those that have been previously exposed. [0049] 10. The resulting solution obtained in step 5, coming from the filter, will now pass to a piece of equipment called the Vial Filling and Sealing Machine, the objective in this step is to dose the filtered solution as quickly as possible into the ampoule's drinkable, always taking care not to wet the neck of the blisters. This machine is will later be in charge of sealing the valves, since it has a system of sealing for this type of blisters. [0050] 11. The next stage is the stage called labeling, stage in which the label is placed label to the product including elementary information such as: Number of Lot, Dosage, Manufacture Date, Expiration Date, etc. [0051] 12. In the final stage of our process, we find ourselves storing our finished product, under favorable conditions of temperature and humidity, characteristic of this type of product. The drinkable ampoules thus obtained according to the process described have a stability 2-year storage environment.

Example 3

[0052] Patients diagnosed with fibromyalgia, arthritis rheumatoid, systemic lupus erythematosus and associated autoimmune diseases with pain and swelling of the muscles and joints, for a period of a month with a dosage of four to six drinkable ampoules per day, with a composition of ingredients per ampoule of:

TABLE-US-00004 Properly Treated Water 19.5%   Dandelion lyophilized extract 30%  Watermelon extract 30%  Mapue extract 8% Licorice Extract 7% Tomato Extract 3% Laurel extract 2% Sodium Benzoate 0.25%   Potassium sorbate 0.25%  

Procedure for the Preparation of an Intramuscular Injectable Solution.

[0053] The procedure for the preparation of an intramuscular injectable solution, consists of the following steps: [0054] 1. In the first stage of the process we receive the different raw materials in the plant, which will go through a process of inspection, classification, and approval to be used in the production of our final product, which will be a intramuscular injectable solution. [0055] 2. After the raw materials have been approved in the receiving area of raw materials, they go to the pre-production area where they are prepared for entry into the production area, it is in this area where they are removed the shell to those raw materials that require it, as well as the seeds, they are cleaned and rinsed with treated water coming from the plant of treatment. [0056] 3. As the raw materials leave this area, they enter the production area where the first piece of equipment or unit operation they enter is a steel mixer stainless steel with temperature control, which is fed with steam, which allows to achieve the temperature increase in it. in this mixer we add all the raw materials of our formula except the Preservative, the Lidocaine and Ascorbic Acid, because these must be added to a temperature from 30° C. to 40° C. to avoid its degradation due to high temperatures and that later they cannot have the expected effect in the final product. [0057] 4. In this mixer the different raw materials all mixed inside the same, they are subjected to a temperature of 96° C. (205° F.), followed by periods of agitation every 5 minutes, this with the aim that at that temperature the water can absorb the properties and nutrients of each of the raw materials present in the mixer, this will allow us to obtain a well charged liquid, rich of all the properties from the herbs, fruits and raw materials that were subjected in this part of our production process. [0058] 5. The resulting solution that comes out of the mixer now goes to another piece of equipment called pressure filter, it is in this equipment where we are going to separate even the smallest solid particle that can be mixed with our solution, the objective in this part of the process is to obtain a solution free of solid particles. In this stage we will take the opportunity to add those pending products that we did not add in the previous stage due to the high temperatures, these are the Preservative, the Lidocaine and Ascorbic Acid. [0059] 6. The container chosen to store the final product is the container: Ampoule of Glass for injectable solutions. [0060] 7. Once these containers leave the washing process, they enter until a sterilization machine or dryer that will oversee sterilizing and drying the containers through the action of high temperatures. [0061] 8. Upon leaving the sterilization machine or dryer, these containers enter a SCT Pharma oven, where the depyrogenation process will be carried out, which is nothing more than that process that will allow us the total or almost total reduction of bacterial endotoxins (pyrogens), in other words what we are looking for is to obtain ampoules free of all microorganisms and undesirable pathogenic substances, this we achieve this through processes that use high temperatures, such as those that have been previously exposed. [0062] 9. The resulting solution we got in step 5, coming from the filter, is now will go to a piece of equipment called the Vial Filling and Sealing Machine, the goal in this step is to dose the filtered solution as quickly as possible into the glass ampoules, always taking care not to wet the neck of the ampoules. This stage will end with the injection of inert gas. This machine will handle after sealing the valves, since it has a sealing system to glass-type ampoules, which were the types of packaging chosen in our process. [0063] 10. Once we have the glass ampoules ready, containing the product inside and properly sealed, they are sterilized, this with the aim of eliminating all possible microorganism or contamination that has remained on the outside of the container during the process, for which sterilization equipment is used called autoclave, the process that is carried out in this equipment is Sterilization By Moist Heat, in which this equipment uses saturated water vapor, at a pressure of 15 pounds which allows the chamber to reach a temperature of 121° C., in this equipment the ampoules will last around 15 minutes crossing the sterilization process. [0064] 11. The next stage is the stage called Labeling, stage in which the label is placed label to the product including elementary information such as: Number of batch, dose, route of administration, manufacturing date, expiration date, etc.

[0065] The ampoules of injectable solution thus obtained according to the described process have ambient storage stability of 2 years.

Example 4

[0066] Patients diagnosed with fibromyalgia, arthritis rheumatoid, systemic lupus erythematosus and associated autoimmune diseases with pain and swelling of the muscles and joints for a period of one month with a dosage of two to four ampoules of solution for injection intramuscular daily, with a composition of ingredients per ampoule of:

TABLE-US-00005 Properly Treated Water 18.01%    Dandelion lyophilized extract 30%  Watermelon extract 30%  Mapue extract 8% Licorice Extract 7% Tomato Extract 3% Laurel extract 2% Lidocaine 1.8%.sup.  Anesthetic Sodium Benzoate 0.17%   Intramuscular Preservative Ascorbic Acid 0.02% 0.02%   Antioxidant

[0067] At the end of the treatment period, a high efficacy of these pharmaceuticals' forms was demonstrated—capsules, tea, drinkable ampoules and ampoules of injectable solution—in improving the comprehensive picture of patients diagnosed with fibromyalgia, arthritis rheumatoid, systemic lupus erythematosus and associated autoimmune diseases with pain and inflammation of muscles and joints headaches and muscular, as well as insomnia and depressive states.

[0068] During the tests, a group of 20 patients were taken and evaluated through of a self-assessment of your condition before starting the plan and after 30 days of treatment, for this assessment they were asked to rate their improvement from 1 to 5 Regarding their situation at the start of treatment, the parameters to be assessed were headaches, muscle aches, joint pains, insomnia and depression. The following table shows the results of the self-assessment of their improvement with treatment.

TABLE-US-00006 TABLE NO. 1 Tabulation of the self-assessment of a sample of 20 patients in the improvement of his individual state of fibromyalgia in this case, with the treatment by a month with the capsules object of the present invention, evaluation of the improvement with a weighting from 1 to 5 Muscular and Headaches joints pains Insomnia Depressive states Patient Before Assessment Before Assessment Before Assessment Before Assessment 1 Yes 4 Yes 5 Yes 5 Yes 4 2 No 0 Yes 5 Yes 5 Yes 4 3 Yes 4 Yes 5 No 0 Yes 4 4 Yes 5 Yes 5 No 0 Yes 4 5 Yes 3 Yes 3 No 0 Yes 5 6 Yes 2 Yes 4 Yes 5 Yes 5 7 Yes 5 Yes 4 Yes 5 Yes 5 8 Yes 5 Yes 4 Yes 5 Yes 5 9 Yes 5 Yes 5 Yes 4 Yes 3 10 Yes 4 Yes 5 Yes 4 Yes 4 11 No 0 Yes 5 Yes 4 Yes 4 12 Yes 4 Yes 5 Yes 4 Yes 4 13 No 0 Yes 3 Yes 4 Yes 5 14 Yes 4 Yes 3 No 0 Yes 5 15 Yes 3 Yes 4 Yes 4 Yes 5 16 Yes 3 Yes 4 Yes 4 No 0 17 Yes 4 Yes 4 No 0 No 0 18 Yes 3 Yes 4 Yes 5 Yes 5 19 Yes 5 Yes 4 Yes 5 Yes 5 20 Yes 5 Yes 4 Yes 5 Yes 5 Rating 4 4.25 4.53 4.5 average Or the improvement

[0069] The results obtained from the self-assessment of each patient who underwent the treatment in the fundamental aspects in which it is manifested diseases such as fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus and autoimmune diseases associated with pain and inflammation of the muscles and joints in just 30 days of treatment is a sample evident that the mechanism of action of these active ingredients is not only to the aspects of relieving pain like other medications that are currently applied for the treatment of this disease as is the case of NSAIDs and opioid derivatives. In the treatment it is verified that the mechanism of action of the quantitative and qualitative combination of active principles not only acts on the nociceptive system but is also an effective anti-inflammatory. in none of the patients who applied the treatment manifested collateral negative reactions.