CN110721175A - Application of curcuma extract in preparation of medicine for treating epilepsy - Google Patents

Abstract

The invention aims to provide a new application of turmeric extract, namely a new application in preparing a medicament for treating human epilepsy. The invention discloses a clinical application method and a curative effect of a turmeric extract as a human antiepileptic and anticonvulsant drug. The turmeric extract can regulate the functions of human bodies by oral administration; increase the therapeutic effect of antiepileptic drugs; the dosage and the side effect of the antiepileptic drug are reduced; and simultaneously, the life quality of epileptics is improved. Furthermore, each component of the turmeric extract is from natural plants, and has no obvious toxicity and side effect on human bodies.

Description

Application of curcuma extract in preparation of medicine for treating epilepsy

Technical Field

The invention relates to application of a compound in medicine, in particular to application of a turmeric extract in preparing a medicine for treating epilepsy.

Background

The Chinese antiepileptic society estimates that about 600 thousands of patients with epilepsy exist in China; at the same time, about 40 ten thousand new epileptic patients occur every year. Epilepsy is one of the most common diseases in neurology. The death risk of epileptics is 2-3 times that of the common population. Before the 80's of the 20 th century, 7 major antiepileptic drugs (AEDs) were used clinically; traditionally referred to as traditional AEDs: carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin sodium, primidone and sodium valproate. After the 80's of the 20 th century, many new AEDs were developed abroad and continuously marketed; for example: felbamate, lamotrigine, levetiracetam tablet, topiramate, vigabatrin.

All of the above antiepileptic drugs have side effects. The severity of these side effects is seen below for the example of carbamazepine and levetiracetam.

Carbamazepine (Cabarmazepine) is a tricyclic anticonvulsant and has been widely used in the treatment of psychiatric disorders in addition to epilepsy, trigeminal neuralgia, dystonia, diabetes insipidus. Due to the wide application of carbamazepine, the toxic and side effects of carbamazepine are increasingly paid attention.

The common reports of nausea, vomiting, appetite change, abdominal distension and constipation caused by carbamazepine are mild and transient reactions, and generally no withdrawal is needed. Liver dysfunction is usually manifested in 5-19% of patients taking carbamazepine, and the symptoms are usually excessive reversible, and few reports of acute cholangitis and bile obstructive jaundice are reported. 3 to 4 percent of patients who take the medicine can have drug eruption, the most common skin damage is eczema, dermatomyositis, exfoliative dermatitis and the like, and the patients can be cured after drug withdrawal, hormone application and symptomatic treatment.

In addition, there are reports of carbamazepine causing leukopenia, agranulocytosis, eosinophilia, thrombocytopenia, aplastic anemia, and recovery after drug withdrawal. It is rarely reported that carbamazepine can directly inhibit erythrocyte uroporphyrinogen-I synthetase, so that porphyrin metabolic disorder is caused, acute interstitial porphyria-like disease is generated, and improvement can be achieved after drug withdrawal. In addition, there have been reports of carbamazepine causing systemic lupus erythematosus, carbamazepine causing neutrophilia, or leukemia-like responses.

In carbamazepine therapy, there are also reports of cardiac rhythm disturbances, conduction blockages and heart failure, often resulting from the damaging effects of drug overdose on the heart. It has been reported that carbamazepine causes nystagmus, slurred mouth, maladjustment, vertigo, lethargy, confusion. Reports of carbamazepine causing hematuria, proteinuria, diabetes and elevated non-protein nitrogen and reduced water excretion, hyponatremia are occasionally reported. Erythromycin can increase the blood concentration of carbamazepine, and even cause toxic reaction. In addition, there are reports of counterpulsation inducing neurotoxic reactions to carbamazepine.

Levetiracetam (Levetiracetam) is an antiepileptic drug, and is mainly used for treating partial seizures of adults and children over 4 years old. The most common side effects are feelings of drowsiness, headache; and symptoms like the common cold. The Qingdao epilepsy research institute summarizes the side effects of levetiracetam as follows.

Systemic reactions and site discomfort of administration: fatigue is common.

Nervous system discomfort: sleepiness is common, and amnesia, ataxia, convulsion, dizziness, headache, hyperkinesia and tremor are common.

Psychologic changes: common irritability, depression, emotional lability, hostility, insomnia, nervousness, personality changes and abnormal thinking. Adverse events were reported after marketing: behavioral abnormalities, aggression, irritability, anxiety, confusion, hallucinations, agitation, mental abnormalities, suicidal ideation, suicide attempts. But there is not enough data to estimate their incidence or to establish causal relationships.

Discomfort of the digestive tract: diarrhea, dyspepsia, nausea, and vomiting are common.

Metabolic and nutritional disorders: often, appetite is diminished. When the patient is taking topiramate at the same time, the risk of appetite loss increases.

Discomfort to the ear and labyrinth: vertigo is common.

Discomfort of the eyes: commonly seen in double vision.

Injury, poisoning and subsequent complications: accidental injuries are common.

Infection and transmission: infection is common.

Respiratory discomfort: an increase in cough is common.

Abnormal changes in skin and subcutaneous tissues: skin rashes are common. After marketing, adverse events reported alopecia, which in some cases recovered by itself after discontinuation of the drug.

Abnormal changes in the blood and lymphatic systems: adverse events reported on the market-leukopenia, neutropenia, pancytopenia, thrombocytopenia, but there is not enough data to estimate their incidence or establish causal relationships.

Turmeric (Turmeric) is a ginger-derived herb with a long-lasting aroma, which is native to India, and has both medicinal and food flavoring effects. The spicy taste is light, and the mixed taste of the sweet orange and the ginger is slightly peppery and bitter. The turmeric is irregular oval, cylindrical or hammer-shaped, is usually bent, has short fork-shaped branches with the length of 2-5 cm and the diameter of 1-3 cm, has dark yellow and rough surface, has crinkle texture and obvious links, and has circular branch marks and fibrous root marks. Firm, hard to break, brown yellow to golden yellow cross section, horny like, and has wax-like luster. The ring veins of the endothelial layer are obvious, and the vascular bundles are scattered in a dotted manner. Special smell, bitter and pungent taste.

Turmeric powder is a powder obtained by grinding dried rhizome of turmeric, is used as a seasoning and a yellow coloring agent, is a common seasoning for household use, and is used for curry powder, seasonings and the like.

Curcumin (curculin) is a chemical component extracted from rhizomes of some plants in the families of Zingiberaceae and Araceae, wherein, turmeric contains about 3-6% of pigment with diketone which is rare in the plant world and is a diketone compound. Curcumin is a yellow acidic phenolic substance and is the main active ingredient of turmeric which plays a pharmacological role. Curcumin has wide pharmacological properties, such as reducing blood lipid, benefiting gallbladder, resisting oxidation, resisting tumor, resisting inflammation, protecting neuron after brain injury, etc. Curcumin is capable of scavenging free radicals, particularly superoxide and hydroxyl radicals.

Curcumin was found to inhibit lipid peroxidation and enhance the antioxidant activity of superoxide dismutase (SOD), glutathione (CSH), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in various in vivo and in vitro experiments. The antioxidant effect of curcumin contributes to its anticonvulsant activity. Studies have shown that not only curcumin: furthermore, the compounds in Curcuma oil also have anticonvulsant effect.

Turmeric, as a plant, has a long medicinal history in different parts of the world, which dates back to 250 b.c. before the era. It is a herbaceous plant used for thousands of years in traditional chinese and india medicine. Today, curcumin is one of the most studied herbs in the world, and its anti-inflammatory and antioxidant effects have been used from arthritis to senile dementia (Alzheimer's).

One of the biggest limitations of natural curcumin is poor absorption after ingestion. This is because turmeric contains two types of secondary metabolites, polyphenolic curcuminoids and hydrophobic essential oils. Polyphenolic curcumin is mainly an oily pigment, since humans are composed of 60% water on average, which means that only a small amount of curcumin is taken into the blood and stays long enough to function.

Epidemiological evidence suggests that turmeric in countries where it is consumed is mixed with foods containing fats and oils, thereby improving the bioavailability of turmeric. The combination of curcumin-lecithin-piperine (pepper extract) also showed enhanced biological activity.

Turmeric extract BCM-95 (biocucumax) is a standardized extract of curcumin made by Arjuna Natural herbal ingredients, india patent. BCM-95 attempts to solve the key problem of increasing curcumin bioavailability by combining 86% curcuminoids [ containing 95% curcumin + 5% (demethoxycurcumin and bisdemethoxycurcumin) ] with 7-9% turmeric essential oil.

Turmeric extract (BCM-95) from DoCas biotechnology (BioTealDoc) was approved by the U.S. FDA as "safe-to-use substance" (GRAS) in food "on 9/13/2016. It is also specified that the maximum amount of extract in food is 180 mg/person per day, and the maximum amount of medical food is 1000 mg/person per day. After GRAS certification, turmeric extract (BCM-95) was introduced into the medical food and food market from the food additive (food supplement) market.

Disclosure of Invention

The invention aims to provide a new application of turmeric extract, namely a new application in preparing a medicament for treating human epilepsy.

Some animal studies have demonstrated the effect of curcumin as an antiepileptic and anticonvulsant; the turmeric essential oil component also has anticonvulsant activity. The neuroprotective, anti-inflammatory and antioxidant properties of curcumin contribute to the treatment of epilepsy and seizures. However, there is currently no clinical study on curcumin as a human antiepileptic and anticonvulsant drug.

The cognitive and joint health benefits of turmeric extract BCM-95 are supported by a number of human clinical studies. The use of turmeric extract BCM-95 to prevent alzheimer's disease is protected by U.S. patent 8859020. However, there is currently no clinical study on turmeric extract BCM-95 as a human antiepileptic and anticonvulsant drug.

The invention discloses a clinical application method and a curative effect of curcumin and turmeric extract BCM-95 as a human antiepileptic and anticonvulsant drug

Detailed Description

To further illustrate the technical solution of the present invention, specific examples are illustrated below.

Curcumin used in this example was a food additive manufactured and tested by NatureBest, uk, with a purity of 95% and a curcumin content of 500mg per tablet.

The turmeric extract BCM-95 (biocucumax) used in this example was a medical food produced by arjuna natural herbal ingredients, india, according to the us patent, and bottled by BioTurm, uk. The components are 86% curcumin compounds [ 95% curcumin + 5% (demethoxycurcumin and bisdemethoxycurcumin) ] and 7-9% turmeric essential oil. Each capsule contains 500mg of BCM-95 Curcuma rhizome extract.

Clinical experiments

Through a volunteer clinical experiment of the applicant of the patent, the invention carries out detailed analysis on the case as follows:

female, age 41. Epilepsy for more than 20 years; first seizure at age 19. Hospitalization was required twice for convulsions. The following antiepileptic drugs were taken for a long time:

8: 00 am: carbamazepine 100 mg; levetiracetam 750mg

1: 00 pm: carbamazepine 150mg

7: 100mg of 00pm carbamazepine; levetiracetam 1000mg

In seizures, the physician may administer therapeutic and sub-therapeutic doses. At therapeutic doses, drugs provide complete protection, while at sub-therapeutic doses they fail to provide complete protection. It is not possible to prevent impairment of learning and memory with sub-therapeutic doses of drugs.

In this case, on the one hand, the physician considers the patient to have an insufficient antiepileptic drug dose; belongs to sub-therapeutic dose. On the other hand, the western medicines have side effects: such as palpitations, dizziness, weakness of the hands, emaciation, and symptoms like the common cold, etc., are very disturbing and annoying to the patient. Thus when the physician recommends increasing the dose to a therapeutic dose; both the patient and her relatives considered the therapeutic dose to exceed her tolerance limits; dose escalation was denied.

The present invention is directed to a method of treatment comprising co-administering a sub-therapeutic dose of an antiepileptic drug with turmeric extract; increase the therapeutic effect of antiepileptic drugs; and simultaneously, the side effect of the antiepileptic drug is reduced.

The co-administration dosage and schedule of the antiepileptic drug and curcumin are as follows:

8: 00 am: carbamazepine 100 mg; levetiracetam 750mg

10: 30am of: curcumin 500mg

1: 00 pm: carbamazepine 150mg

4: 00 pm: curcumin 500mg

7: 100mg of 00pm carbamazepine; levetiracetam 1000mg

The arrangement maintains the difference between curcumin and other drugs for at least 2.5-3 hours; to avoid drug interactions.

The curcumin dose escalation process is as follows:

week 1: 4pm per day: curcumin 250 mg (half tablet)

Week 2-15: 4pm per day: curcumin 500mg (one tablet)

Week 16: 10 parts per day: 30am of: curcumin 250 mg (half tablet); 4pm per day: curcumin 500mg (one tablet)

Week 17-30: 10 parts per day: 30am of: curcumin 500mg (one tablet); 4pm per day: curcumin 500mg (one tablet)

The above schedule is that of starting with 250 mg (half a tablet) of curcumin per day and continuing for the week. If no adverse effects were observed, the dose of 250 mg (half tablets) per day was gradually increased weekly until a dose of 1000mg (two tablets) per day was reached 2 times per day.

The co-administration of the antiepileptic drug with turmeric extract BCM-95 was dosed and scheduled as follows:

8: 00 am: carbamazepine 100 mg; levetiracetam 750mg

10: 30am of: BCM-95 Capsule 500mg

1: 00 pm: carbamazepine 150mg

4: 00 pm: BCM-95 Capsule 500mg

7: 100mg of 00pm carbamazepine; levetiracetam 1000mg

The above arrangement maintains the difference between BCM-95 of Curcuma longa extract and other drugs for at least 2.5-3 hours; to avoid drug interactions.

The gradual increase process of the turmeric extract BCM-95 dosage is as follows:

week 1: 4pm per day: BCM-95 Capsule 500mg

10.30am per day on weeks 2-4: BCM-95 capsules 500 mg; 4pm per day: BCM-95 Capsule 500mg

The above schedule is from BCM-95 once a day; 500mg (one capsule)/day on, and continue for the week. If no side effects were observed, then BCM-95 was increased to twice daily; 1000mg (two capsules)/day.

Patients continued to use curcumin for about 7 months, and then changed to continuous use of BCM-95 capsules (1 month until the filing date of this patent). The curative effect is summarized as follows:

the medical clinical experiment proves that:

curcumin and turmeric essential oil have effects as antiepileptic and anticonvulsant for humans. The neuroprotective, anti-inflammatory and antioxidant properties of turmeric are helpful in the treatment of epilepsy and seizures in humans.

The combination of turmeric extract and antiepileptic drug can reduce the dosage of antiepileptic drug.

The combination administration of the turmeric extract and the antiepileptic drug can reduce the side effects of the antiepileptic drug.

The combination administration of turmeric extract and antiepileptic drug can improve the life quality of epileptic patients.

In conclusion, the turmeric extract can regulate the functions of the human body by oral administration; increase the therapeutic effect of antiepileptic drugs; reducing the dosage and side effects of antiepileptic drugs; and simultaneously, the life quality of epileptics is improved. And each component of the turmeric extract is from natural plants, has no obvious toxicity and side effect on human bodies, meets the condition of the invention patent, and the invention patent application is proposed according to the law.

Claims (5)

1. A novel medicament for the treatment of epilepsy, characterized by: curcumin is an effective component of the novel medicament for treating epilepsy.

2. A novel medicament for the treatment of epilepsy, characterized by: curcumin is the main component of the new epilepsy treating medicine.

3. A novel medicament for the treatment of epilepsy, characterized by: the turmeric extract is the effective component of the new medicine for treating epilepsy.

4. A novel medicament for the treatment of epilepsy, characterized by: the turmeric extract is the main component of the new medicine for treating epilepsy.

5. A novel medicament according to claims 1.2.3 and 4 for the treatment of epilepsy, characterized by: the medicine is prepared into all pharmaceutically allowable dosage forms.