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Patent Searching and Data


Title:
DRUG GOOD FOR USE IN TUBES OR CATHETERS PLACED IN STOMACH AND INTESTINES
Document Type and Number:
WIPO Patent Application WO/2018/063128
Kind Code:
A2
Abstract:
The invention relates to patients unable to take food orally so drugs (1) required to be taken orally given through tubes or catheters (5), and the drugs (1) used for such patients in health sector. The invention particularly relates to drugs (1) which can be given to patients unable to take drug orally, by means of tube or catheters (5) placed in stomach and intestines of such patients wherein the size of the said drugs (1) is smaller than inner diameter of the said tubes or catheters (5).

Inventors:
EREL KAMIL VARLIK (TR)
ÖZŞİŞECİ LATIFE (TR)
Application Number:
TR2017/050349
Publication Date:
April 05, 2018
Filing Date:
July 26, 2017
Export Citation:
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Assignee:
EREL KAMIL VARLIK (TR)
OEZSISECI LATIFE (TR)
Other References:
None
Attorney, Agent or Firm:
DESTEK PATENT, INC (Nilüfer/Bursa, TR)
Download PDF:
Claims:
CLAIMS

1. Drug (1 ) which can be given to patients unable to feed orally, through tubes or catheters (5) placed in their stomach and intestines and which have sizes smaller than inner diameter of the said tubes or catheters (5) in such manner that they can pass through the said tubes or catheters (5).

2. A drug (1 ) according to claim 1 and it is characterized in that the said drug (1 ) capsule form as micro - capsule has

- length of (a): 5 - 10 mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm.

3. A drug (1 ) according to claim 1 and it is characterized in that the said drug (1 ) enteric coated tablet form as micro - enteric coated globe has

- diameter of (c ): 1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm.

4. A drug (1 ) according to claim 1 and it is characterized in that the said drug (1 ) enteric coated tablet form as micro - enteric coated tablet has

- length of (a): 5 - 10 mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm. 5. A drug (1 ) according to any of claims 1 - 4 and it is characterized in that the said drug (1 ) is a late release drug taken orally.

Description:
DESCRIPTION

Drugs good for taking through tubes or catheters placed in stomach and intestines

The Related Art

The invention relates to patients unable to take food orally so drugs required to be taken orally given through tubes or catheters, and the drugs used for such patients in health sector. The invention particularly relates to drugs which can be given to patients unable to take drug orally, by means of tube or catheters located in stomach and intestines of such patients wherein the size of the said drugs is smaller than inner diameter of the said tubes or catheters. Background of the Invention

Today the calorie needs and drug taking of patients unable to be fed orally are provided through feeding tubes. Application of nutrition support orally or through gastrointestinal system is called enteral feeding. Enteral feeding tubes can be applied into stomach, duodenum or jejunum. The ones which are most frequently used for feeding purpose are naso - gastric and naso - enteric tubes.

When the patient is unable to swallow, enteral feeding is also used for drug administration purpose. However, during drug administration through feeding tube, it is needed to prevent blocking in the feeding tube and reduction in drug effect and minimize the drug toxicity risk by use of appropriate methods. For the patients unable to take drug orally, first of all, alternative drug administration ways such as intravenous, intramuscular, subcutaneous, inhale, transdermal, rectal ways are preferred. However, where the alternative administration ways are not convenient and it is required to give drug orally, drug administration through enteral feeding tube is used. On the other hand, sizes of the drug on market are not of the sizes allowing passing through such tubes and catheters. For instance, the drugs required to be taken regularly or instantly due to current disease, by patients hospitalized at intensive care unit and unable to feed themselves because of systematic diseases (antihypertensive, antiparkinson, antiepileptic, Alzheimer etc.) can be given by crushing and decomposition by means of nasogastric, orogastric feeding tubes or pag tubes placed in stomach of the patients.

In drug administrations with feeding tubes, current fluid dosage forms of the drug or broken and crushed tablet and capsule form in solid dosage are used. As a result of faulty use of drugs from enteral feeding tube in this way, complications such as blocking in tube, decreased drug effectiveness or increasing toxicity can be seen.

Drug is the chemical composition administered for recovery from or prevention of diseases. Most of drugs used by patients for routine chronic diseases or current disease they suffer from are produced by means of various methods to slow down the release in order to ensure slow and long time absorption in duodenum instead of stomach, or in further small intestine parts. However, due to their big sizes, the drugs in intensive cares are crushed into powder and administered through the said catheters and tubes (feeding tubes). Slow release cannot be provided because the coated agents are also crushed and the protection around the drug is not provided. Therefore, the expected effect is not gained in terms of both time and blood level.

Solid dosage forms of the drugs are divided into two, namely capsules and tablets. In coated tablets, the tablets are coated with a polymer film or sugar in order to protect the active substance against light, air and humidity, to enhance strength during packaging and handling, to facilitate swallowing for patient, to prevent stomach irritation, to ensure protection of active substance against gastric secretions or to change release properties of the active substance. It should be careful during administering coated tablets through enteral feeding tube. The tablets coated only to improve appearance of the tablet and capsulate not having good taste are crushed when administering through enteral feeding tube. However, when tablets coated to protect against humidity, light and air are crushed, the active substance's stability may be lost. In case the tablets coated in order to conduct controlled release and protect the drug from gastric irritation are crushed, release properties of the drug may change and cause blocking in tube.

Late released drugs are formulated to release the active substance at a time after administration of the drug. Release of delayed release drug in small intestine (in enteric coated dosage forms) or in colon (dosages specific to colon) can be controlled. Enteric coated tablets are designed to release the drug in intestine in order to prevent decomposition of drug due to acidic conditions of he stomach and minimize the side effects that might occur in stomach. Thus late start of effect is provided. If the distal end of the enteral feeding tube is in stomach, then such drugs should not be crushed. Because the stability of the drug will be lost and probability of gastrointestinal irritation will increase. When administering drug through feeding tube, the amount of absorbed drug may decrease. If distal end of the enteral feeding tube is inside small intestine (duodenum or jejunum), problem in terms of efficiency of the drug is encountered. However, when enteric coated tablets are crushed and administered through enteral feeding tube, small particles may cause blocking in the tube.

Some experienced cases indicating requirement and importance of nasogastric and nasoduodenal form are given below as example.

CASE 1 : Patient suffering from epilepsy, having attacks, not taking drug orally, with nasogastric feeding, film coated capsule is broken (crushed) before giving. Drug has never reached required blood level. Frequency of attacks was increased on the 3 rd day and the patient had to be intubated and given anaesthesia.

CASE 2: Patient suffering from tuberculosis was given medicine by nasogastrict tube as he did not take medicine orally. Since the drug was given after opening the capsule and was affected by stomach acid, the drug was not effective and the patient is ex.

CASE 3: No effective result was obtained because the drug was opened and given orally to the patient had metabolic acidosis diagnostic and suffering from kidney disease in nephrology treatment. The patient had to be taken for dialyzing.

CASE 4: The patient suffering from high blood pressure not able to take drug orally was given film coated high blood pressure drug through nasagastrict but was not effective to reduce pressure. It had to be started giving medicine intravenously for high blood pressure.

CASE 5: Since stomach protector drugs required to be taken orally are given by opening the capsules, it has not been effective. It was required to give the drug intravenously. In the related art, the drugs required to be given orally and no other alternative administration ways to patients unable to take drug orally are given to patients by means of above mentioned feeding tubes. The sizes of the drugs are bigger than the inner diameter of the tubes used in health sector. Therefore, the said drugs cannot be given through tubes unless they are broken and crushed. And such administration causes failure to gain the effect expected from the drugs. Furthermore, blocking of tubes is a frequently encountered case.

As a result, due to above described disadvantages and inadequacy of existing solutions it has been necessary to make development in the related art.

Brief Description of the Invention

The present invention relates to a drug convenient for use through tubes or catheters located in stomach and intestine and meeting the needs mentioned above, eliminating all disadvantages and providing some additional advantages.

The primary purpose of the invention is to ensure that the patients unable to take drug orally can take drugs required to be given orally without conducting any action such as breaking, crushing powdering the drug etc.

The invention aims to develop drug of sizes allowing use through a tube or catheter orally.

Another purpose of the invention is to provide sizes of late release drugs required to be given orally appropriate for giving through feeding tubes or catheters.

Another purpose of the invention is to ensure that the effectiveness of the drugs given to patients by means of feeding tubes/catheters is the same as effectiveness of drugs directly given orally without use of tube.

A further purpose of the invention is to provide that the drugs required to be taken orally have smaller sizes than inner diameter of tubes or catheters placed in stomach or intestines of patients. In order to achieve the above purposes the invention relates to drug which can be given to patients unable to be fed orally through tube or catheter placed in stomach and intestines of patients and which has sizes smaller than inner diameter of the said tube or catheter to allow passing through the said tube or catheter.

In order to achieve the purposes of the invention,

• Capsule form of the said drug as microcapsule has

Length of (a): 5 - 10 mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm,

• Enteric coated tablet form of the said drug as micro - enteric coated globe has

- diameter of (c ): 1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm,

• Enteric coated tablet form of the said drug as micro - enteric coated tablet has - length of (a): 5 - 10 mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm.

In order to achieve the purposes of the invention, the said drug is a late release micro or small drug used orally.

The structural and characteristic features and all advantages of the invention will be understood better in the figures given below and the detailed description by reference to the figures. Therefore, the assessment should be made based on the figures and taking into account the detailed descriptions.

Brief Description of the Drawings

Figure 1 is cross - section view of tablet form of the drug.

Figure 2 is side view of tablet form of the drug.

Figure 3 is cross - section view of capsule form of the drug.

Figure 4 is side view of capsule form of the drug.

Figure 5 is crossed - section view of enteric coated tablet form of the drug as microenteric coated globe. Figure 6 is comprehensive view of enteric coated tablet form of the drug as

microenteric coated globe.

Figure 7 is schematic view of drug's passing through tube or catheter. The drawings are not necessarily to be scaled and the details not necessary for understanding the present invention might have been neglected. In addition, the components which are equivalent to great extent at least or have equivalent functions at least have been assigned the same number. Description of Part References

1 . Drug

5. Tube/ catheter

a. length

b. width

c. diameter

d. enteric coated thickness

Detailed Description of the Invention

In this detailed description, the drug (1 ) good for use through tubes or catheters (5) placed in stomach and intestines and preferred embodiments thereof disclosed hereunder have been described in a manner not forming any restrictive effect and only for purpose of better understanding of the matter.

The invention relates to drugs (1 ) which can be given to patients through tubes or catheters (5) placed in stomach and intestines of patients and have sizes smaller than inner diameter of the said tubes or catheters (5). The said drugs (1 ) are constituted of drugs (1 ) in capsule or tablet form in sizes allowing passing through the tubes or catheters (5) and not allowing crushing, produced as enteric coated or nano - technologically. Figure 7 shows schematic view indicating the drugs' (1 ) way of passing through tube or catheter (5).

The inner - outer diameters of tubes and catheters (5) used in health field are generally as follows. Nasogastric and feeding catheters

• 14fr: 4,67 mm (inner) - 5,67 mm (outer)

• 16fr: 5,33 mm (inner) - 6,33 mm (outer)

• 18fr: 6,0 mm (inner) - 7,00 mm (outer)

PEG (percutaneous endoscopic gastrostomy ) tubes

• 16fr: 5,3 mm (inner)

• 20fr: 6,7 mm (inner)

In terms of size, the drug (1 ) disclosed hereunder is of size allowing easily passes through these tubes or catheters (5).

The drug (1 ) disclosed hereunder in the form of capsule or tablet is of the following sizes.

• In capsule form as microcapsule;

- length of (a): 5 - 10mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm,

• Enteric coated tablet form as micro - enteric coated bal,

- diameter of (c ): 1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm,

• Enteric coated tablet form as micro - enteric coated tablet,

- length of (a): 5 - 10 mm,

- width of (b): 0.1 - 3 mm,

- enteric coating thickness of (d): 0.01 - 0.1 mm,

Capsule is the form in which the hard and fluid drugs are offered in market in cylinder, round or olive - like shapes in gelatine protectors. They have types melting in stomach or intestines.

Tablet is the way of offering the drugs in powder in cut cylinder or round shapes after compacting. Figures 1 - 6 show the views of tablet and capsule forms of the drug (1 ) disclosed hereunder. To assist the production in the above given sizes, the drugs (1 ) of such sizes can be produced by use of other nano - technological methods (micosphere, microcapsule, micro - emulsion, nano - capsule, nano - sphere, nano - emulsion etc.).

Production method for the drug (1 ) disclosed hereunder, in general, consists of process steps of

• Obtaining as compressed in microglobe, microcapsule or microtablet form by applying pressure to the drug (1 ) in micro forms,

· Film coating in film coating unit.

In microtablet production, powder drug raw material is exposed to following steps by use of existing conventional methods. · Homogenization

1 . Density designation for density

2. Flow test

3. Sieve analysis

4. Microscope analysis

5. Sedimentation designation

• Granulation

In order to convert homogenized drug powder particles into tablet in next step, granulation which is the production of drug pellets which are final products is performed.

Wet granulation method

Production stage of solid drug forms consists of several steps. In wet granulation process which is the first step of them, the agents of binding nature are added to powder mixtures and powder particles aggregation is provided. This method consists of the following general procedure steps.

- active substance (if deemed necessary ) grinding

- Mixing powder agents,

-Adding bonders and aggregation of powder mixture particles (this procedure is called granulation.) - Wet sieving aggregated particles,

- Drying sieved powder mixture, use of flowing bearing dryers commonly in drying procedure,

- dry grinding after completion of drying,

- Homogenization in double conical or V - type mixers,

- Adding lubricant to the resulting mixture and mixing it for 5 minutes (mixture becoming convenient for tablet step is called final product.

Extrusion Pelletizinq

This method is a mechanic method achieved by means of subjecting globe granules to different stages in order to obtain globe granules of same or similar size. Firstly, powder agents are mixed dry. Granulation is carried out by wetting. Then the granules of global co - particle sizes is obtained by means of passing the mass in sludge form through holes of certain diameter upon compressing. This method is the method of preparing granule by wet method, compressing under pressure (extrusion) to convert into a certain form and finally to globe.

When wet granulation method is applied, hole diameters for producing micro tablet and obtain pellettes of drug sizes to be estimated before coating are designed according to sizes to be produced.

Dry granulation method

Dry granulation is conducted through two different methods. They are pre - compression (slugging method) and roller compaction method.

The drug and auxiliary agents are get into granule form without wetting or drying. This method is preferred for drugs sensitive to heat. Granulation is compacted by mechanic compaction. The compaction is achieved by slug tablet preparation and breaking or passing of powders through rotating steel rollers. This method consists of the following general procedure steps.

- Pre - mixing (drug and auxiliary agents)

- Powder compaction (slug tablet formation/rotating steel rollers)

- Breaking - grinding/ - sieving

- Lubricant addition and short time mixing This method contains less basic procedures. It requires special manufacturing devices and makes granule manufacturing of high density possible for high dosage drugs. - Pre - Compression Method

In rotary tablet machines where high pressure can be applied, part or all of powder agents are converted into big tablet by pre - compression after dry blending without dosage adjustment. Then tablets are broken by a convenient crusher and sieved by sieves of certain opening and made into particulates of desired size. The variability between powder preparations granulated in different boilers by this method is considerably low. Control parameters during and after the process are low. Efficiency in respect to time is high. Equipment variability is little and power consumption is low.

In the production of the drug (1 ) disclosed hereunder if dry granulation pre - compression method is used, instead of current sieve openings used for micro - tablet production, sieve openings according to micro tablet forms estimated before coating are used.

- Roller Compaction Method

It is a dry granulation method in which previously dry blended powder or powder mix is compressed and passing through the opening adjusted between two rollers moving in counter directions. The obtained compacted mass is sieved to gain desired particle size. When dry granulation roller compaction method is used in production of the drug (1 ) disclosed hereunder, sieve sizes matching micro tablet forms calculated before coating in order to produce micro tablet and obtain pellets in the drug sizes calculated before is preferred. Tablet Production and Coating Methods

Preparation of tablet mix by wet granulation method consists of the following procedure steps:

- effective and binding agents are put into wet granulation tank. - Upon spraying and adding bonding agents onto active substance, active substance becomes big size more fluid and compressible granule.

- Mass in wet form is sieved as a wet form by sieve connected to granulator tank. Sieved wet granules are sent to fluid bearing boxes by help of vacuum.

- The granules dried at certain temperature and time is sieved dry by hammer mill and all granules are made of the same size.

- After adding filling agents and auxiliary agents, blend for a certain time with tumbling or V mixers.

- Lubricant is added to the mass close before end of mixing and mixing is continued for further 5 - 10 minutes

- Samples are taken from certain points of homogenized tablet press mixing and sent to laboratory.

- After result of homogenous is obtained at the laboratory, mixture is sent for tablet press.

Preparation of tablet mix by dry granulation method consists of the following procedure steps:

- Active substance and bonder and filling agents are ground.

- Ground powder mixture is compacted between rollers and briquette is obtained.

- Powder mixture in briquette form is crushed, milled and sieved,

- Sieved powder mixture is subjected to a short mixing,

- Lubricant is added to mixture of a certain granulate size and mixture is conducted for a while,

- It is sent for tablet press.

Tablet Formulation Machines

Tablet presses can be classified as single punch (eccentric) type and industrial type multi punch rotary or rotary presses. The system, called as station, consisting of one upper punch, one lower punch and one die. Tablet press machines have turrets variable according to shape of tablet. Convenient micro - turrets are used to obtain micro tablets of the sizes calculated before coating Tablet coating

The products such as micro tablet globe etc. obtained therefrom are coated with the material intended to be coated on the drug by use of spraying or dipping into boiler. A different lack of the drug sector will be eliminated by means of this invention. The said deficits experienced in patients treatments are eliminated and thus butter conditions are provided The said problems are frequently seen for all late released drugs mainly for cardiovascular system, endocrine, neurology, respiratory, gastrointestinal systems.

The invention is developed for patients who are unable to take drug (1 ) orally but must take crushed drugs (1 ) through nasogastric catheter (feeding catheter placed in stomach through nose) or percutaneous endoscopic gastrostomy (stomach tube placed in stomach through skin via endoscope PEG) placed in stomach and intestines . Crushing drugs (1 ) changes dissolution place, absorption places of drug (1 ) in digestion system and their effect time. The invention relates to production and design of drug (1 ) in size matching inner diameter of the said catheters or tubes (5) so as to administer the said drugs (1 ) without crushing but in the form they are produced, without affecting bioavailability, biotransformation, effect and absorption time.