WO2010071951A1

WO2010071951A1 - Pharmaceutical composition

Info

Publication number: WO2010071951A1
Application number: PCT/BR2009/000415
Authority: WO
Inventors: Marino Renan
Original assignee: Farmacia E Laboratório Homeopático Almeida Prado Ltda.
Priority date: 2008-12-22
Filing date: 2009-12-22
Publication date: 2010-07-01
Also published as: BRPI0805555A2

Abstract

The present invention provides a homeopathic pharmaceutical composition consisting of a synergistic combination of Crotalus horridus, Eupatorium perfoliatum and Phosphorus which, when used in association, reduce the intensity of dengue fever symptoms, besides preventing haemorrhagic complications.

Description

PHARMACEUTICAL COMPOSITION

Field of the Invention

The present invention relates to a homeopathic pharmaceutical composition for use as an aid in the symptomatic treatment of dengue, substantially improving tiredness, discouragement, malaise, headache, muscle pain, nausea, inappetence, fevers and chills, abdominal pain and retro pain. -eye.

State of the art

Dengue is a short-term acute infectious disease of varying severity, acute and benign fever, with an incubation period of 5 to 8 days, caused by an arbovirus of the genus Flavivirus. Classical dengue is usually benign. Infection caused by any of the four types of dengue virus produces the same manifestations. Determining the type of dengue virus that caused the infection is irrelevant to treating the sick person. Dengue is a disease that, in the vast majority of cases, causes discomfort and inconvenience, but does not endanger people's lives. It begins with high fever and may present with headache, prostration, myalgia, muscle pain, retroorbital pain, nausea, vomiting, abdominal pain. It is common that, 3 to 4 days after the onset of fever, red spots on the skin, similar to those of measles or rubella, and itching occur. It is also common for minor bleeding, especially on the nose and gums.

Most people, after four or five days, start and improve and recover completely, gradually, in about ten days.

In some cases, within the first three days after the fever begins to subside, a marked decrease in blood pressure may occur. This drop in pressure characterizes the most severe form of the disease, called "hemorrhagic" dengue fever. This name may make you think that bleeding always occurs, which is not true. Severity is mainly related to lowering blood pressure, which should be treated quickly as it can lead to death. Severe dengue can occur even in those who have the disease for the first time. The hemorrhagic form presents high mortality, especially in children.

The patient recovers, usually without any problems. It is also immunized against the type of virus that caused the disease. However, you may get sick again with the other types of dengue virus.

Aedes aegypti, the most important vector in the Americas, reproduces easily in still water containers, but dengue can also be transmitted by the Aedes albopictus mosquito.

Aedes aegypti belongs to the Culicidae family, which has two interdependent ecological phases: the aquatic, which includes three developmental stages - egg, larva and pupa - and the terrestrial, which corresponds to the adult mosquito.

Epidemics usually occur in summer, during or immediately after rainy periods. Dengue is rapidly expanding, and the major concern is that transmission in the coming years will increase throughout tropical areas of the world if effective measures are not taken to contain epidemics.

It is believed that in the coming years the southern countries of

Europe could again be hit by dengue and other mosquito-borne tropical diseases due to global warming.

Considering World Health Organization estimates that dengue affects at least 50 million people a year in more than 100 countries on all continents, it is assumed that dengue epidemics have indeed grown in size and virulence, which may suggest that the virus has mutated into a more resistant type.

Thus, in the medium term, the only hope for facing the Outbreaks of the disease are due to the control of the mosquito population, with the aggravation that the two vector species represented by Aedes aegypti and Aedes albopictus, have shown incredible adaptation to urban environments, and quickly develop immunity to insecticide use including the aerosols.

Dengue diagnosis is based on epidemiological and clinical data. The virus can be isolated in the blood in the early days of the disease. Serological tests may be performed: hemagglutination inhibition, complement fixation and seroneutralization. Prophylaxis is limited only to the fight against Aedes aegypti, and dengue vaccine production is still under research.

In interviews with the International Herald Tribune, Duane Gubler, senior scientific research advisor for the Vector-borne Infectious Diseases Division of the US Centers for Disease Control, noted that very little is known about the dengue virus, complicating the fact. of presenting with four different varieties, which represents a considerable obstacle in research focused on the production of an effective dengue vaccine. Several vaccines are currently in the testing phase that are expected to last several years, and the focus has to be on mapping the dengue virus genome so that the drugs are developed with the ability to inhibit its replication in the body. human.

Currently, the only treatment to alleviate the symptoms caused by dengue is the use of acetaminophen. Acetaminophen or acetaminophen, as it is known in the United States, is an extremely useful medicine in cases of fever and pain. However, as its analgesic effect is less efficient, the tendency is to increase the dosage, which can cause, besides kidney damage, an irreversible liver injury that may even require transplantation of this organ. And it is not difficult to achieve this overdose because it is a less active pain reliever and is present in other medications as with almost all influenza.

An adult cannot take more than 4 grams of acetaminophen per day. If you take two 750 mg tablets, because one is too little to combat the pain you are feeling, you have already taken 1, 5 g. He then decides to take two of the best-selling flu pills that have 400 mg of acetaminophen each. By repeating the medication three times in one day, the risk of intoxication increases considerably.

It is also important to note that Dengue is a disease that causes liver problems and if paracetamol is not used with caution, there is a risk of precipitating a very serious liver problem.

Summary of the Invention

The present invention provides a homeopathic pharmaceutical composition consisting of the synergistic combination of the elements Crotalus horridus, Eupatorium perfoliatum and Phosphorus, which when used in combination attenuate the intensity of dengue symptoms and prevent hemorrhagic complications.

Still more preferably, the homeopathic pharmaceutical composition comprises Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal (DH) and centesimal (CH) scales, and also, Lactose, Cellulose and Vegetable Magnesium Stearate.

Homeopathic pharmaceutical compositions start from isolated dynamizations of each substance, and each element among Crotalus horridus, Eupatorium perfoliatum and Phosphorus can be dynamized in ranges from 1 DH to 1 million DH and from 1 CH to 1 million CH.

Preferably, the homeopathic elements of the present invention such as Crotalus horridus, Eupatorium perfoliatum and Phosphorus are present in the 10 DH to 35 DH and 10 CH to 30 CH dynamizations. In another aspect, the present invention provides a homeopathic pharmaceutical composition based on the elements Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH10) and / or centesimal scales (CH10).

In another aspect, the present invention provides a homeopathic pharmaceutical composition Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH15) and / or centesimal scales (CH15).

In another aspect, the present invention provides a homeopathic pharmaceutical composition Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH20) and / or centesimal scales (CH20).

In another aspect, the present invention provides a homeopathic pharmaceutical composition Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH25) and / or centesimal scales (CH25).

In another aspect, the present invention provides a homeopathic pharmaceutical composition Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH30) and / or centesimal scales (CH30).

In a further aspect, the present invention provides a homeopathic pharmaceutical composition Crotalus horridus, Eupatorium perfoliatum and Phosphorus, dynamized on decimal scales (DH35).

The present invention further provides a method of administering the pharmaceutical composition which may be effected in two distinct ways: (i) for prevention; when the patient uses a dose of 30 tablets over 10 days and repeats this dose within 6 months; (ii) to relieve dengue symptoms; when the patient only uses the 30 tablet dose over 10 days, when infected with disease.

Detailed Description of the Invention

The present invention provides a homeopathic pharmaceutical composition consisting of the synergistic combination of Crotalus horridus, Eupatorium perfoliatum and Phosphorus, which when used in combination attenuate the intensity of dengue symptoms in addition to preventing bleeding complications.

The present homeopathic pharmaceutical composition is present in a base of lactose, cellulose and vegetable magnesium stearate or alcoholic solution or in sucrose.

It is also important to note that the homeopathic pharmaceutical composition may be in all pharmacopoeial pharmaceutical forms, particularly in the form of tablets, drops, tablets and globules.

Each 0.250 g tablet of this composition has a formulation as per Table 1.

Crotalus 0.008 horridus ml

0.009

Eupatorium perfoliatum

ml

0.008

Phosphorus

ml

0.250

Lactose, cellulose and vegetable magnesium stearate qsp ...

g

For a better understanding of the range of action of homeopathic medicine, follow Table 2, based on the work of ossak-Romanach.

Tabe 2

Activity Primary Phase Secondary Phase Remarks

There is only the phase

. LETHAL - Irreversible.

primary

The ability of ultra-diluted substances to transmit an order and information, according to Bohmv's concept, similarly to the use of weighted doses, has represented the greatest challenge to be overcome by homeopathy. However, this phenomenon has long been demonstrated in extensive production of laboratory research using homeopathic dynamizations. Currently we find a large volume of publications that confirm the action of ultra dilutions. We will cite for special interest Ullman, who reports on the work of Boiron et al., Published in 1983, evaluating basophil degranulation from the use of Histaminum 7 CH and Apis 7 CH from the serum of allergic patients.

The drugs that integrate the homeopathic anti-dengue complex, as detailed below, pathogenically cover the predominant symptoms in dengue and hemorrhagic fever.

The active Eupatorium perfoliatum represents the typical condition of classical dengue, while the active Phosphorus exerts, through its hepatotropic action, the maintenance of the organ's functional integrity and the production of coagulation factors, and finally, the active Crotalus horridus that corresponds to the most common synthesis. similar to dengue hemorrhagic symptoms.

The combination of Eupatorium perfoliatum + Phosphorus + Crotalus horridus obeys dengue-related epidemiological criteria and the technique of selection of the best homeopathic drug adapted to the epidemic, also called the epidemic genius technique. There is consensus on homeopathy, which is the primary choice for medicines by similarity.

The dynamizations of Crotalus horridus, Eupatorium perfoliatum and Phosphorus can range from CH1 to CH1 million and from DH1 to DH 1 million.

Powers classified as low or medium, ie, between 6 and 12 CH, equivalent to 12 and 24 DH, have preference when dealing with acute conditions such as the case, besides presenting results of remarkable activity confirmed in the experimentation stage. add prompt and effective action, with no adverse effects.

Thus, the choice of 15 power in decimal scale or Hering is preferred and is due to present the same prompt and consistent biological action as demonstrated by the experimental results.

Example of Preparation of 15D Streamlined Homeopathic Pharmaceutical Composition

Initially the workbench should be properly cleaned using 70% alcohol. In a 1000 ml amber flask containing 630 ml 96% alcohol, 70 ml Crotalus horridus 14DH is added with the aid of a graduated glass beaker to the flask, capped and labeled and taken to the electrical equipment. mechanical electronic 180M dynamizer (mechanical arm) for 100 succussions, obtaining Crotalus horridus 15DH.

In a 000 ml amber flask containing 630 ml 96% alcohol, 70 ml Eupatorium perfoliatum 14DH is added with the aid of a graduated glass beaker to the flask, capped and identified and taken to the electrical apparatus. mechanical electronic 180M dynamizer (mechanical arm) for the accomplishment of the 100 succussions, obtaining Eupatorium perfoliatum 15DH.

In a 1000 ml amber flask containing 630 ml of 45% alcohol, 70 ml of Phosphorus 14DH is added with the aid of a graduated glass beaker to the flask, capped and labeled and taken to the electro-electronic equipment. mechanical 180M dynamizer (mechanical arm) for the accomplishment of the 00 sucussions, obtaining Phosphorus 15DH.

After preparation, a 100 ml sample of the active ingredient is separated, with 50 ml going to the Chemical Physical Quality Control and 50 ml to the Microbiological Control for analysis, together with the request for analysis.

The glasses containing the active ingredients are labeled with the yellow quarantine label, in plastic boxes identified in the "Liquid Preparation Room", awaiting the release of the Quality Controls.

Upon approval the active inputs receive the green approved label.

In the drops sector, the person in charge of the Order of

Production, separates the requested quantities of dynamized liquids (matrices) and crushed into powders (matrices), already approved by the Quality Control, sending them, duly identified, to the weighing sector.

In the weighing sector, the person responsible for cleaning the area where the inert inputs will be weighed, according to the specific Production Order Planning, starting the weighing operation. All operations are recorded and all inputs receive labels identifying them.

After weighing all the raw materials for the manufacture of the batch, they are sent to the heavy raw materials room, where they are packed, grouped, duly identified with Analysis Bulletin and identification tag, on pallets, together with the Order. of production. The active inputs (Dynamized) are in plastic boxes, in these same pallets, grouped.

In the production sector, the employee must be properly dressed, he identifies the room. The employee checks all the raw materials he received. It must attach to the Production Order, the labels of the raw materials, checking them and signing the Production Order. They must attach all documents relating to the cleanliness of the room and equipment.

Lactose and Cellulose is passed through Tamil No. 28 and added to the Kneader where it remains for 5 minutes under stirring. The liquid dynamized (matrices) are impregnated and, where appropriate, the crushed powders (matrices), respecting the proportion of 10% (FHB), as determined in the formula, in the Production Order.

At the end of the impregnation period, the entire mixture remains under stirring for a further 30 minutes.

The powder obtained is stored in stainless steel trays lined with parchment paper, properly identified and taken to the Greenhouse. The powder will be subjected to a temperature below 50 ° C for a period of 4 hours, according to specific POP, for drying. Remove the dried powder from the Greenhouse,

The product is then re-sieved in size # 8 in the kneader where Magnesium Stearate is mixed for 3 minutes.

After mixing is transferred to containers (buckets) plastic bags lined internally and properly identified. The product, in buckets, is transferred to the bulk product room awaiting the release of the compression cabin.

Once in the compression cabinet, the product is placed in the machine and the compression process begins. The compression process is continued for a short period, sufficient to obtain sufficient sampling. The process is interrupted for analysis by the Chemical Physical Quality Control. A 35 g sample is sent from the start of compression along with the request for analysis. After approval and clearance by the Chemical Physical Quality Control, the process is continued.

During the compression process, every 15 minutes, the average tablet weight and hardness, the ambient temperature and humidity are checked by the compression worker and recorded on the Process Control form.

During the process, 35g samples from the process medium as well as 35g samples in the final phase of the compression process are taken and sent to the Chemical Physical Quality Control for analysis for the purpose of recording the process control. In total there are 105 g of samples per batch for Process Control by Chemical Physical Quality Control.

A Quality Control employee can randomly sample the process tablets. In the compression sector she can analyze average weight and average hardness by recording in the Process Control chart by rubric.

The tablets are collected in plastic bag-lined containers and are identified and proceed to the bulk tablet room at the end of the process. The approved batch remains in the bulk pill room awaiting the Packaging process.

The Production Order is completed by the employee of each sector, being finalized by the pharmacist responsible for the sector. In all processes the Production Order accompanies the product and all labels are attached to the Production Order. The person in charge of the packaging sector in the Production Order checks and checks the product and that there is no trace of another product in the room. Each line and room is cleared through a check list. The room is identified with the room identification tag.

Packaging staff properly dressed in cap, gloves, mask, apron and prop. The warehouse worker should take the batch of semi-finished product to packing room IV. The employee of Packaging IV must check the material received and register in the Production Order.

The warehouse clerk should bring the entire package item to the packing room IV and the packaging clerk IV should check all incoming material by registering in Production Order.

The packaging employee IV must affix the batch identification sheets to the packaging line. The IV packaging clerk assigned to the packaging must manually accommodate the tablets within the transparent blisters, each blister having 14 spaces.

The blister should be placed inside the double cork cradle and taken to the blister, following the specific procedure POPPE-0 6. The blister packs are accommodated in pre-cleaned yellow plastic boxes and with the product identification sheet.

After packing all the Product tablets in the blisters, the yellow boxes containing the product should be sent to the packaging room I so that the blister packs with the product can be stamped on the Ink Je Willett.

The person responsible for packaging IV shall designate a official to stamp the blisters on the packaging I following the procedure POPPE-010, with the authorization and supervision of the person in charge of the packaging sector 1, since it must have the packaging line released by the Quality Assurance, without the presence of another product. The blisters are encoded with the batch number, date of manufacture and expiration date. The employee prints the data in a blank space on the Production Order and the packaging officer IV requests a Warranty representative to check the data printed on the "test blisters" with the Production Order and after approval release the equipment for printing, signing and dating a blister.

After all blisters have been stamped on "Ink Jef Willett Eq-001 following POPPE-010, the designated employee must carry the yellow boxes containing the already stamped blisters back to packaging IV to continue the secondary packaging process, ie the blisters should be placed inside the cartridges.

The packaging officer IV shall designate a sector official to stamp the cartridges in packaging I following the specific procedure POPPE-009, with the authorization and supervision of the packaging officer 1.

Packaging I must have the packaging line released by Quality Assurance, without the presence of another product. There may be inkjet identification on the blisters of the same product and same lot in this room at the same time.

Cartridges are encoded with lot number, date of manufacture and expiration date. The packaging officer IV requests a Warranty representative to check the data printed on the "test cartridges" with the Production Order and after approval release the equipment for printing by signing and dating a cartridge. Must attach this cartridge signed on the Production Order.

After all cartridges are stamped on the "stamper" Eq-003 following the ΡΟΡΡΕ-0Ό9, the designated employee must return the stamped cartridges back to packing area IV to continue the secondary packing process.

IV packaging staff must manually put into the envelope: 1 blister (with the blister containing 30 tablets) and a package insert. IV packaging personnel should close and accommodate product boxes in pre-cleaned yellow plastic boxes.

The packaged cartridges are removed from the yellow boxes and begin to receive the security seals manually on both sides and are placed on the table. After receiving the security seal, they must be re-accommodated in yellow plastic boxes marked with the product name, batch number, date of manufacture and expiration, number of boxes and signature of the responsible person.

48 units of the finished product are withdrawn, 24 units being sent to the Chemical Physical Quality Control and 24 units to the Micro Biological Quality Control, together with the request for analysis. All yellow boxes receive the yellow "QUARANTINE" seal

The person in charge of packaging IV must record all process steps, quantities produced, leftovers and losses of products and packaging material in the Production Order.

Chemical physical properties of pharmaceutical composition

Feature Specifications

Appearance White or almost white

Average weight 231.25 mg-268.75 mg Reliability <1.5%

Hardness 3.0 to 5.0 Kgf

Disintegration <10 minutes

Diameter 9 mm

Height 4-4.2 mm

Claims

1. Homeopathic PHARMACEUTICAL COMPOSITION for the treatment of dengue characterized by comprising the homeopathic elements Crotalus horridus, Eupatorium perfoliatum and Phosphorus in dynamization ranges Indo from 1 DH to 1 million DH, from 1 CH to 1 million CR

Homeopathic PHARMACEUTICAL COMPOSITION according to Claim 1, characterized in that it comprises the homeopathic elements Crotalus horridus, Eupatorium perfoliatum and Phosphorus in dynamization ranges from 10 DH to 35 DH.

Homeopathic PHARMACEUTICAL COMPOSITION according to Claims 1 to 2, characterized in that it comprises the homeopathic elements Crotalus horridus, Crotalus horridus, Eupatorium perfoliatum and Phosphorus on the dynamization scale of 15 DH.

Homeopathic PHARMACEUTICAL COMPOSITION according to any of Claims 1 to 3, characterized in that it is in all pharmacopoeial pharmaceutical forms, particularly in the form of tablets, drops, tablets and globules.

Homeopathic PHARMACEUTICAL COMPOSITION according to Claims 1 to 4, characterized in that it is present in a base of lactose, cellulose and vegetable magnesium stearate or in alcoholic solution or in sucrose.