FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
PATENTS RULES, 2003
(COMPLETE SPECIFICATION)
TITLE OF INVENTION- "A CUSTOMIZABLE DOSING SYSTEM FOR MORNING SICKNESS."
NAME OF APPLICANT- ZOTA HEALTH CARE LTD
ADDRESS OF APPLICANT- ZOTA HEALTH CARE LTD
ZOTA HOUSE,
2/896, HIRA MODI STREET, SAGRAMPURA, SURAT 395002, (GUJARAT) INDIA.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention relates to customizable dosing system for morning sickness specifically for pregnant women. This combination is totally safe for fetus also.
BACKGROUND OF THE INVENTION
Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed, the exact cause remains unclear. Nausea and vomiting of pregnancy begins between the fourth and seventh week after the last menstrual period in 80 percent of pregnant women and resolves by the 20th week of gestation in all but 10 percent of these women.
Several effective prescription medications have been widely used in pregnancy with no proved evidence of harm to the fetus or the mother. This may include Vitamin B6, ondansetron, promethazine, prochlorperazine, metoclopramide, Diphenhydramine, Meclizine and trimethobenzamide. FDCs are also prescribed like Vitamin B6 + doxylamine.
Meclozine is a first-generation antihistamine of the piperazine class. Meclozine is an antihistamine considered to be an antiemetic. It is sold under the brand names Bonine, Bonamine, Antivert, Postafen, Sea Legs, and Dramamine (Less Drowsy Formulation). Emesafene is a combination of meclozine and pyridoxine . In Canada, Antivert Tab (which is no longer available) was a combination of meclozine and nicotinic acid.
The proposed invention not only overcomes the various limitations of the existing medicine or drugs but can also be configured to achieve specific dosage.
Some existing inventions are following-
6,586,023 wherein A method for producing a coated chewing gum with a controlled release of an active agent, as well as the chewing gum so produced, is obtained by physically modifying an active agent's properties by coating and drying. An active agent is coated by encapsulation, partially coated by agglomeration, entrapped by absorption, or treated by multiple steps of encapsulation, agglomeration, and absorption. The coated active agent is then co-dried and particle sized to produce a release-modified active agent. When

incorporated into a chewing gum coating, these particles release into the mouth but mask bitter and other off-tastes in the mouth, and are readily ingested.
WO2012003350 wherein A method of delivering a health care active having the steps of administering to a mammal in need of a health benefit or a treatment for a health condition a personal health care article and consuming the article. The article contains one or more filaments that contain a backbone material, a health care active and optionally aesthetic agents, extensional aids, plasticizers, and crosslinking agents.
Patent application number: 20090142443 wherein Some embodiments of the present invention include multi-region chewing gum compositions containing at least one active in a solid candy composition and an elastomer region, specifically where the active is caffeine. Methods of masking off-tastes of active ingredients are provided. Further, methods pf manufacturing a caffeinated solid candy center fill gum composition are provided. Methods of delivering a dosage of caffeine to a user of the gum composition are additionally provided.
JP6248357 wherein A solid pharmaceutical preparation comprising a pharmaceutically active ingredient, erythritol, crystalline cellulose and a disintegrants, which exhibits a fast buccal disintegratability and dissolubility.
SUMMARY OF THE INVENTION
The object of the invention is to provide a quick and efficient medication for pregnant
woman.
The object of the invention is to provide that the some existing medication caused birth
defects, which was proved wrong later.
The object of the invention is to provide that the previous combination of Diphenhydramine
and Meclizine causes drowsiness.
The object of the invention is to provide that Promethazine contained combination causes
drowsiness and dry mouth. Rare side effects include muscle contractions that cause twisting
or jerking movements. (Anti cholinergic effects )
The object of the invention is to provide that Ondansetron contained combination might be
effective but it is one of the most expensive anti-nausea medications.

The object of the invention is to provide that one of the ingredient Vitamin B6 can reduce symptoms of mild to moderate nausea, but do not usually help with vomiting.
DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail in connection with certain preferred and optional embodiments. So that various aspects thereof may be more fully understood and appreciated.
The exact cause of nausea and vomiting in pregnancy is not clear. Most evidence points to rapid changes in hormone levels. These fluctuations may cause changes in the muscle contraction and relaxation patterns of stomach and intestines, thus leading to nausea and vomiting.
The hormones that seem to have the most to do with this process include the pregnancy hormone human chorionic gonadotropin (hCG), estrogen, and progesterone. Abnormal levels of thyroid hormones have also been reported in women with severe vomiting, although a cause-and-effect relationship remains unclear. Some studies have shown that nausea is worse when your blood sugar level is low.
The present invention discloses the efficiency pharmaceutical composition in oral dosage form. This comprises therapeutically effective amount of Meclizine, Vitamin B6 and Caffeine with suitable excipients so as to make the formulation stable.
According to the oral pharmaceutical composition of the present invention, the said oral pharmaceutical composition is available in various forms such as tablet, capsule, sachet, powder (liquid), candy, chew gum thereof.
In embodiment of the invention, as per the Pharmacodynamics Meclizine, a piperazine-derivative H1-receptor antagonist similar to buclizine, cyclizine, and hydroxyzine, is used as an antivertigo/antiemetic agent. Meclizine is used in the management of nausea, vomiting, and dizziness associated with vertigo in diseases affecting the vestibular apparatus. It possesses anticholinergic, central nervous system depressant, and local anesthetic effects. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the

medullary chemoreceptor trigger zone.Meclozine may be effective in relieving vertigo experienced as a result of inner ear infections or other conditions.
The main mechanism is that Antihistamines decrease the nausea sensation by blocking H1 receptors in the emetic center and decreasing sensitivity of the vestibular apparatus within the inner ear. In addition to antihistaminic activity, these compounds possess anticholinergic activity; meclizine has an onset of action of about one hour with a prolonged duration of action; drug effects can last anywhere between 8 to 24 hours following oral administration with a half life of 6 hours. Based on studies conducted on rats, meclizine is metabolized to an inactive metabolite, norchlorcyclizine, most likely by the liver. Norchlorcyclizine distributes throughout all body tissues of the rat, as well as penetrating the placental barrier. Meclizine is found unchanged in the feces, but was eliminated as norchlorcyclizine in the urine.
Morning sickness, is also called pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased estrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or hormone replacement therapy. Sometimes it is present in the early hours of the morning and reduces as the day progresses. The nausea can be mild or induce actual vomiting, however, not severe enough to cause metabolic derangement. In more severe cases, vomiting may cause dehydration, weight loss, alkalosis and hypokalemia. This condition is known as hyperemesis gravidarum and occurs in about 1% of all pregnancies. Nausea and vomiting can be one of the first signs of pregnancy and usually begins around the 6th week of pregnancy (counting gestational age from 14 days before conception). In spite of its common name, it can occur at any time of the day, and for most women it may stop around the 12th week of pregnancy.
In embodiment of the invention, Vitamin B6 is a water-soluble vitamin, however unlike other water-soluble vitamins; vitamin B6 can be extensively stored in the body's muscle tissues. Vitamin B6 comes in 3 forms being 'pyridoxal', 'pyridoxine' and 'pyridoxamine', helps your body metabolize protein, fats, and carbohydrates. It also helps form new red blood cells, antibodies, and neurotransmitters, and is vital to your baby's developing brain and nervous system.It has also been shown to influence cognitive performance (through serotonin production) and steroid hormone activity. During pregnancy there is a deficiency of pyridoxal phosphate due to progesterone hormone. It also causes neural excitability, can be subsided with exogenous Vitamin B6.

Extra vitamin B6 may relieve nausea or vomiting. Some natural sources also available such as Beans, nuts, lean meat, and fish are good sources of vitamin B6. {Note that a 3-ounce serving of meat or fish is about the size of a deck of cards.) Fortified breads and cereals can also be good sources but vitamin B6 is required in a special amount in different condition for example Pregnant women need only 1.9 milligrams (mg) of this vitamin a day to help make antibodies, red blood cells, and neurotransmitters and to meet the needs of their developing baby. Vitamin B6 is found in a wide variety of foods so you may satisfy this requirement by eating a nutritious diet. (Prenatal vitamins contain B6 as well.)However, the dose commonly recommended for easing nausea and vomiting is much higher - 10 to 25 mg, three times a day. Normal daily recommended dose of vitamin B6 is 10 to 25 mg three times per day during pregnancy, whereas the current dose used in this FDC is 3 times lesser than the normally prescribed dose. Vitamin B6 being water soluble vitamin, excess vitamin B6 will be excreted out of body in urine, thereby reducing the chances of accumulation toxicity to minimum.( during pregnancy reduction of pyridoxal phosphate ,can be replenish by vitamin B6)
In embodiment of the invention, Caffeine that moderate levels of caffeine have not been found to have a negative effect on pregnancy. The definition of moderate varies anywhere from 150 mg - 300 mg a day. Caffeine is a central nervous system and metabolic stimulant, and is used both recreationally and medically to reduce physical fatigue and to restore alertness when drowsiness occurs. It produces increased wakefulness, faster and clearer flow of thought, increased focus, and better general body coordination. Experts have stated that moderate levels of caffeine have not been found to have a negative effect on pregnancy. The definition of moderate varies anywhere from 150 mg - 300 mg a day. Whereas the caffeine's dose which is being used in current FDC is only 10 mg, which is 15 times lesser than the lower limit of the daily allowed dose during pregnancy.
In embodiment of the invention, beta cyclodextrine has the best balance of enhanced aqueous solubility, a wide range of drugs with which it forms stable complexes, and the most extensive collection of safety data in the technical literature with no adverse reactions reported. It gives better teast. One of the important property of Beta-Cyclodextrin is that it makes much more hemolytic and irritating when administered intramuscularly or topically to mucous membranes.

CLAIM
We claim,
1. A customizable dosing system comprises therapeutically effective amount of Meclizine, Vitamin B6 and Caffeine with suitable excipients so as to make the formulation stable.
2. A customizable dosing system as claimed as claim 1 wherein Meclizine is used in the management of nausea, vomiting, and dizziness associated with vertigo in diseases affecting the vestibular apparatus. It possesses anticholinergic, central nervous system depressant, and local anesthetic effects
3. A customizable dosing system as claimed as claim 2 wherein It possesses anticholinergic, central nervous system depressant, and local anesthetic effects. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone.
4. A customizable dosing system as claimed as claim 3 wherein Meclozine may be effective in relieving vertigo experienced as a result of inner ear infections or other conditions.
5. A customizable dosing system as claimed as claim 1 wherein it can be very use full in controlling pregnancy induced nausea and vomiting.
6. A customizable dosing system as claimed as claim 1 wherein Vitamin B6 also acting as a mild to moderate anti emetic, synergistically increases the effects of meclizine in controlling pregnancy induced nausea and vomiting and also helps in the prevention of anemia, improves immunity and cognitive function.
7. A customizable dosing system as claimed as claim 6 wherein the major importance of Vitamin B6 is that during pregnancy there is a deficiency of pyridoxal phosphate due to progesterone hormone. It also causes neural excitability, can be subsided with exogenous Vitamin B6.
8. A customizable dosing system as claimed as claim 1 wherein it is reducing the chances of side effects due to caffeine combination to minimum, making well

balanced to act effectively and synergistically in controlling nausea and vomiting associated with pregnancy.
9. A customizable dosing system as claimed as claim 8 wherein Addition quantity of caffeine is suitable for subside the anticholinergic side effects of meclizine.
10. A customizable dosing system as claimed as claim 2 wherein the dose of meclizine is 5 times lesser than the normally prescribed dose during pregnancy and caffeine's dose (caffeine which is acting as neutralizing agent for the meclizine's antihistamine side effect drowsiness and thereby keeping the person alert) being 10 times lesser than the normally allowed daily dose during pregnancy.