Patent Application
20180021556
The present invention relates to intradermal, subcutaneous or intramuscular drug delivery. More particularly, the present invention relates to rapidly implanting an active pharmaceutical ingredient into the body painlessly.
Administration of drug into human bodies is one of the most important interventions in medical treatment and disease prevention. There are two general drug administration routes that are commonly practiced, namely enteral and parenteral drug administration. The enteral administration route involves the esophagus, stomach, and intestines and parenteral administration route involves injection and infusion by needles. The most common enteral administration is oral administration (i.e. eating or drinking the drug). The advantage of this route is that it is easy to do, but the disadvantage is that the drug may be disintegrated or degraded by the gastro-intestinal tract and therefore much higher dose is needed, which may be toxic to the body. For this reason, all biologics are not suitable to be administered orally because the gastro-intestinal tract will digest or degrade them.
On the other hand, parenteral administration generally involves injection or infusion via cannulas, which includes subcutaneous, intradermal, intramuscular and intravenous injections using stainless steel needles. Parenteral injections avoid the gastro-intestinal tract so is ideal for biological drugs such as peptides, hormones, vaccines and antibodies. Its other advantages are fixed and accurate doses and short administration times, normally within 3-5 seconds for injections (except for infusion). Its main disadvantage is the pain incurred during the short period of time. The pain associated with parenteral injections is caused by two separate actions, namely the insertion of needle and the injection of liquid into the body. There is a long-felt need to eliminate the pain caused by parenteral injections.
Microneedles were invented to provide a solution to eliminate the pain due to parenteral injections. There are two kinds of microneedles: the first kind is solid microneedles in which drug is loaded on the microneedles and is delivered to the body when the microneedles penetrate into the skin; another kind is hollow microneedles in which drugs are injected into the skin through the hollow microneedles. The insertion of solid and hollow microneedles is quite painless due to the micron-size of the microneedles. But due to the size of the solid microneedles, the amount of the drug which can be loaded on the microneedles is very limited.
As a matter of fact, there are many problems associated with delivering drug using solid microneedles. For example, there are commonly two ways to load the drugs on the solid microneedles: (a) the drugs may be coated on the surface of non-dissolving microneedles or (b) the drugs may be mixed with dissolving materials such as hyaluronic acid and moulded into dissolvable microneedles. The solid microneedles by the first method, apart from having limited drug loading capacity, is not able to deliver complete dose because the coated drug will come off the needles' surface and stay outside the skin. The U.S. Pat. No. 8,361,022 B2 awarded to Alza Corp. and U.S. Pat. No. 7,846,488 B2 awarded to 3M Innovative Properties Company reported the inventions involving the coating of drugs on solid microneedles.
The second method to load drugs on the solid microneedles is to mix the drug with the dissolving material and mould the mixture into dissolvable microneedles. The dissolving materials may be hyaluronic acid, chitosans, hydrogels and other polymers that dissolve upon making contact with the skin. Among other problems, the paramount issue is that the drug mixture becomes a new form of drug and therefore requires separate clinical approval if the drugs involved are controlled by the regulatory bodies. This imposes great impedance for the technology to reach the market because the clinical trials involved are lengthy and expensive, and each drug has to undergo a new drug approval process. U.S. Pat. No. 8,167,852 B2 awarded to Cosmed Pharmaceutical Co. Ltd and U.S. Pat. No. 8,506,980 B2 awarded to Bioserentach Co. Ltd reported inventions related to this type of microneedles.
We mentioned earlier that drugs can also be injected via hollow microneedles. In this case, the insertion of hollow microneedles into the skin is quite painless and they can continuously inject liquid drugs into the skin, which in this case increase tremendously the deliverable amount of the drug. But the injection of liquid via hollow microneedles into the skin causes pain, and since the hollow microneedles' injection rate is much lower than that of the conventional cannulas, the pain is felt much longer (the delivery time for 0.5 ml is 5-30 minutes for hollow microneedles compared to 3-5 seconds for cannulas). Therefore, microneedles do not totally solve the pain associated with parenteral injections. PCT application WO 2011/014514A1, which was filed by 3M Innovative Properties Company reported such a technology.
There is yet another new technology developed by Glide Pharma involves inserting a drug load at a few metre per second with the help of a pioneer projectile, which is made of a biodegradable material. Typical drug may not have the required hardness for penetrating the skin, so a biodegradable pioneer projectile, which has sufficient hardness to penetrate the skin, is used as an ‘introducer’ for allowing the drug load to enter the skin. The introduction of a foreign material into the skin for the purpose of drug delivery may not be desirable. The foreign material, although biodegradable, may be considered as a new excipient and makes the drug a new drug, which is then subjected to new drug registration process.
It can be seen that the current drug administration techniques including enteral, parenteral and microneedle administrations fail to provide a painless and high-dose drug administration platform. To achieve these three requirements, a device has to be designed to address these three issues, which are inter-dependent.
To start with, a substantial drug loading capacity has to be viable to fulfil most dosage (a few micro grams to a few milligrams), which should be achieved without introducing any new excipients because any new mixture will be treated as a new drug. A typical drug load of these dosages normally amounts to a few nanolitres to a few microliters of volume, which must be transported into the body painlessly. Injecting drug loads at this size into the body will certainly cause pain because the body will need to make space for the drug load which is foreign to the body.
Secondly, the delivery of the drug load should be done as quickly as possible. Currently the parenteral injections are done within 3-5 seconds and the new delivery system should not take more than that because the psychological stress under which a patient is subjected may be too huge and one second more may be unacceptable to the patient. Lastly and most importantly, the rapid delivery of substantial drug load has to be carried out painlessly, otherwise such a device is no better than current needles and syringes.
There is a long-felt need in administering drug to a body painlessly, rapidly, and completely. The present invention seeks to provide a solution for drug administration to the body which is painless, rapid and high dosing.
The present invention provides a solution for addressing the design requirements for delivering drug rapidly and painlessly with high and complete dose, which cannot be achieved by microneedles or conventional needles. The present invention relates to a drug implant device which delivers a drug load to a body painlessly. The present invention achieves the drug implantation by adopting two principles: (1) rapid perpendicular insertion of fine cannula is painless and that (2) pain is incurred only when the occupied volume caused by the implant process is increased. Therefore, instead of inserting a cannula and injecting a volume of drug, which increases the additional volume for accommodating the additional volume of the drug during the injection process (i.e. the occupied volume), the present invention retracts the cannula in order to dispose expose the drug into the body. The retraction of cannula does not increase the occupied volume therefore incurs no pain. (In fact, it reduces the occupied volume of the implant process.)
The present invention involves essentially rapid perpendicular insertion of a small amount of drug into the body intradermally, subcutaneously or intramuscularly in a painless manner. In the first preferred embodiment 100, the present invention comprises a fine cannula 300, which has a beveled tip for rapidly penetrating the body, a drug load 320 and an inner rod 340, wherein the drug load 320 and the inner rod 340 are slidably disposed within the cannula 300 and that the drug load 320 is disposed at the beveled end of the cannula 300 (i.e. the forward position) while the inner rod 340 is disposed adjacent to the drug load 320 (i.e. the rearward position). When the first preferred embodiment 100 is in use, the cannula 300, the drug load 320 and the inner rod 340 are rapidly inserted together into the body (in a substantially perpendicular manner in order to eliminate pain) so that the drug load 320 is transported to the desired depth, after which the cannula 300 is retracted while the inner rod 340 and the drug load 320 remain stationary relative to the cannula 300, thereby disposing the drug load 320 at the desired depth of the body, and after which the cannula 300 and the inner rod 340 are fully removed from the body.
The first preferred embodiment 100 may be used with a spring applicator 500 for achieving the desired insertion speed. The spring applicator 500 comprises a slidable casing 520, a transparent cap 540, a returning spring 560, an actuation spring 580, a button 600, and a vault 620. When in operation, device 100 is inserted into spring applicator 500 and is attached to the vault 620. Next, the slidable casing 520 is pulled backward to compress the actuation spring 580, the returning spring 560 will return the slidable casing 520 back to its original position. Lastly, button 600 is depressed to release the vault 620 and the actuation spring 580 will propel the device 100 with the desired speed for rapid insertion.
In the second embodiment, the drug implanting device 1000, a simplified version of the first preferred embodiment is provided. The drug implanting device 1000 comprises a top casing 1100a, a bottom casing 1100b, a lever button 1200 disposed on the top casing 1100a, a compression spring 1300, a cannula 1400, a cannula holder 1500 on which the cannula 1400 is fastened, an inner rod 1600 slidably disposed within the cannula 1600, a rod stopper 1700 on which the inner rod 1600 is fastened, and a drug load 1800 disposed within the tip of the cannula 1400.
The present invention aims to provide a painless means to deliver a sizeable drug load into the body. As discussed previously, the injection method is painful, partially due to the insertion of the needle into a body, but more significantly due to injecting a finite volume of drug into the body, which has to make space for that finite volume. The present invention achieves its objectives by two principles. The first principle is that when a cannula is rapidly inserted into the body in a substantially perpendicular manner, provided that the size is small enough, i.e. gauge size of 27 G to 34 G, i.e. with outer diameter between 0.4 mm-0.18 mm and that the insertion speed exceeds 1 m/s, the insertion of the cannula into the body is quite painless. Therefore, the present invention incorporates a rapid perpendicular insertion of cannula to eliminate pain due to needle insertion.
The second principle is that pain is incurred only when the occupied volume caused by the implantation is increased; for example, injecting liquid drug into the body increases the occupied volume as the body needs to make space for the liquid, which causes pain. Instead of injecting any drug, which causes the body to make up the occupied volume for the drug (which is very painful), the present invention pre-loads a drug load 320 in the cannula 300 and rapidly inserts the drug-loaded cannula 300 into a body, after which the cannula 300 is retracted while keeping the drug load 320 in the body. This is achieved by having an inner rod 340 which is disposed in the cannula 300 to hold the drug load 320 in place during the retraction of the cannula 300. In this way, the occupied volume caused by the insertion of the cannula 300 does not increase, but it actually decreases after the cannula 300 is retracted, causing no pain. Once the drug load 300 is disposed in the body, it is wetted by the interstitial fluid in the tissue and is fused to the tissue in the body and will not leave the body easily. Finally, the cannula 300 and the inner rod 340 are removed from the body completely.
It is worth noting that while the insertion of the cannula 300 requires high speed, such as 1 m/s or more, the retraction of cannula 300 requires much lesser speed to prevent the drug load 320 from ‘splashing’ when the cannula 300 retracts. The reason is that the drug load 320 is always in physical contact with the inner surface of the cannula 300, if the cannula 300 retracts in high speed, the surface friction will pull the drug load 320 together, the consequences are a portion of drug may stay in the cannula, and that the drug load 320 may be dispersed to other undesirable depths, causing the drug delivery un-controllable. The retraction speed can be achieved by reducing the actuation speed provided by a compression spring 280. The speed reduction method may be employing a sliding piston that remains in good contact with the stationary surface during sliding, dampening the initial actuation force of the compression spring 280. The sliding pistons are made of silicone rubber, or any material that is able to provide firm contacts between sliding surfaces. The retraction speed for the cannula should be less than 20 mm/s to ensure good implant quality.
The present invention incorporating these two principles can be represented by two preferred embodiments, which are discussed in the following paragraphs.
Now, we will describe the first preferred embodiment of the present invention. In
The device 100 relies on manual insertion.
The trigger 200 serves to conceal the cannula 300 when not in use. As the trigger 200 continues to be pushed rearward, it engages and unlatches the slider 220; as a result, the compressed compression spring 280 releases its potential energy and pushes rearward the slider 220, which is fastened to the second piston 260 and the cannula 300, sliding on the sliding slot 160. This action retracts the cannula 300 while it is still in the body, disposing the drug load 320 to the body. The compression spring 280 continues to push the slider 220 and the second piston 260 rearward until the second piston 260 hits the first piston 240, after which both pistons 240, 260 move rearward together. As the two pistons 240, 260 move rearward together, the cannula 300 and the inner rod 340 retract from the body together completely. This completes the drug implant process. The implanted drug load is properly disposed in the desired depth, normally within penetration depth of 1 mm-25 mm under the skin.
It is vital to understand the exact mechanism of how the implant of drug load into a body can be achieved.
The first preferred embodiment of the present invention can be used with a spring loaded applicator, which is shown in
There is a need to provide a simpler device to carry out the drug implant function in the present invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/SG2015/050022 | 2/13/2015 | WO | 00 |
