CN1163578A - Needle-less parenteral introduction device - Google Patents

Abstract

A needle-less device for the parenteral administration of a medicament is disclosed. The medicament has the shape of one end of a toothpick. It is palced in the bore of a barrel with the barrel having the shape of a nose cone at one end. A plunger is inserted into the other end of the bore. The plunger forces the medicament through the skin and into the subcutaneous layer of the patient without the need for penetration of the skin by a needle.

Description

Needle-less parenteral introduction device

Scope of the present invention

The present invention relates to parenteral introduction device, this device is in particular for the administration of muscle or subcutaneous medicament active compound.

Background of the present invention

In many cases, non-stomach intestine medicine-feeding is better than oral administration.For example, can under the situation that gastrointestinal tract is partially or completely degraded, should adopt non-stomach intestine medicine-feeding at the medicine of being given.Similarly, when in case of emergency needing medicine onset immediately, common non-stomach intestine medicine-feeding also is better than oral administration.

Though in many application, all wish to use the parenteral introduction approach at present, it also truly have many drawbacks.Perhaps Zui Da drawback is exactly can cause patient's discomfort to patient's administration the time.The preparation of general parenteral introduction contains a large amount of suspendibles or the required liquid of dissolved substance.The ratio of active component and carrier is generally at 1: 100 to 1: 1000.Run into low dissolving of active component or very difficult suspendible, under perhaps many heavy dose of administration situations, perhaps above-mentioned two kinds when having concurrently, more need to inject a large amount of liquid.Acupuncture treatment and import a large amount of liquid and can make parenteral introduction bring pain more or less or be uncomfortable at least to patient.And solvent or suspensoid itself also might cause pain.

With liquid as pharmaceutical carrier administration to also have a shortcoming be that medicine is usually unstable in liquid.Like this, medicine and liquid should be prepared when injection temporarily.This also is a very big drawback, and for example, many diseases are to cure the disease to need many days the course of treatment for the treatment of.

So, if can find one neither to need method that pin do not need liquid solution or suspension yet just highly significant.

The known solid mixture that is useful on the parenteral introduction of may command drug dose release, the device that does not need liquid direct injection medicine, used trocar when imbedding thing or pill as insertion, and a device described in the European patent, European Patent Application No. 0292936A3, these devices be used for injecting solid.Trocar and European Patent Application No. are that the device described in the 0292936A3 all needs to use pin.

The present invention's general introduction

The applicant has invented a kind of more cheap device that non-gastrointestinal approach gives solid or semi-solid medicament that passes through.This device does not need to use pin fully, but with piston boit solid drugs is directly injected patient's skin, and as the human or animal, the degree that piston boit enters skin is just injected skin with medicine and got final product.Medicine can be made the shape of toothpick end, promptly have a wedge angle then to gradually become cylinder at the one end.This medicine needs certain rigidity, so that parenteral introduction device of the present invention medicine when administration can enter hypodermic layer by transdermal.So, the discomfort that entry needle brings to patient when not having parenteral introduction when the medicine transdermal.This device also has an automaton, wherein can contain some parts of medicines, can give a plurality of patients administration one by one by this device.

By following diagram, detailed description and claims can also be recognized other characteristics of the present invention and advantage.

Illustrated simple description

Fig. 1 is the cutaway view of parenteral introduction device of the present invention;

Fig. 2 is the form of the retracted mode of parenteral introduction device of the present invention before its administration;

Figure 3 shows that the situation when apparatus of the present invention are injected patient with medicine.

Fig. 4 has the device of an automatic system for the present invention, and wherein piston boit is replaced by Compressed Gas;

Figure 5 shows that another automaton, this device can be injected medicine in some patient bodies successively.

Detailed description

At first look at Fig. 1, this figure is the profile of parenteral introduction device of the present invention, by three Individual basic part forms, and namely main barrel 10, sleeve 12 and piston boit 14. Main tube 10 One central duct 16 is arranged, and its aperture one end is at tube 22 places, and other end opening is at tube 20 places. Medicine 18 is loaded in the centre bore 16. Also have outstanding ring 24 and 26 on the main bucket 10, lower Face can be talked about ring fixation. Sleeve 12 is at its top 28 and the ends 30 place's opening. Sleeve Ledge 32 and 34 are arranged on 12, and also can talk about below it mainly is moving of restriction sleeve Moving. Piston boit 14 has piston rod 36 and distal end cap 38. One disk 40 is arranged on the distal end cap 38 And flank 42. The external diameter of piston boit 36 should be at least identical with the internal diameter in duct 16 or Slightly little.

Figure 2 shows that the form after the assembling of parenteral introduction device of Fig. 1, also can should Form is transported and is stocked. The rear end 28 of sleeve 12 is pressed and is attached on the piston boit 14. To be enclosed within Sleeve 12 on the tube 10 pushes downwards, makes its shoulder prominent 32 slip over ring prominent 24 and sleeve is solid Fix on the position of ring prominent 26. Sleeve be by slip cap on the outer surface of main tube 10. Shoulder prominent 32 and ring prominent 26 be in conjunction with can fixed muffle 12 and the relative position of main tube 10, this Sample can not released main bucket 10 ends 22 with medicine 18 because making because of carelessness piston boit 14. Ring Prominent 24 is to stop because carelessness makes sleeve 12 and main tube 10 to throw off because sleeve 12 with Ring was dashed forward and can be stuck on the position of shoulder prominent 32 before main tube 10 was separated from.

Plug 44 is made by biocompatible substance, and as cellulose or gelatin, plug is enclosed in the end 22 of main tube 10 to guarantee that medicine can be not contaminated before administration.In addition, whole device also can be stocked in an aseptic environments, in foil paper or cellophane.(not diagram).

Figure 3 shows that just in use a device.One end 22 of main tube 10 overlays on curing the disease people's skin 48, and applies certain pressure should for the medicine injection site.Piston boit 14 of Hua Donging and sleeve 12 be by exerting pressure on piston boit 14 distal end cap 38 together, make they along main tube 10 to lower slider, slide into shoulder prominent 34 and prominent 24 position contacting of ring.Piston boit 36 runs through the total length in the duct 16 of main bucket 10, and extruding medicine 18 passes patient skin 48 and enters hypodermic layer 46.The shoulder of sleeve 12 prominent 34 with limited the sliding scale of piston boit 36 in master tins 10 after the ring prominent 24 of main tube 10 combine.The position of piston boit 36 should not exceed more than the main bucket 10 1 end 222mm, and preferably the position of piston boit does not exceed the end 22 of main bucket 10 at all.

Figure 4 shows that another kind of form of the present invention.In this device, piston 14 is substituted by air pressure, and air pressure is provided by valve 54 by an air drain 52.Medicine 18 passes bucket 56 under the pressure of gas.Replaceable bucket 56 after the per injection.Button 58 back injectables once.This can make air-flow discharge by valve 54 and actuator 60 from air drain 52, pushes medicine 18 then and enters patient's (not shown) by bucket 56.In this automaton, because the size that puts on the medicine upward pressure is by actuator 60 controls, so pressure is always the same.Like this, any power of the power of injection and operator all has nothing to do.

Fig. 5 is another form of Fig. 4 automated injection device.Use this device can be continuously give a plurality of dosage of a plurality of patient injection medicine and not more changing device only use one to get final product.Device shown in Figure 5 has a batch pan 62, and dish has many ducts 64, and medicine 18 is contained in each duct 64.As shown in Figure 4, press push button 58 back air pressure can inject patient with medicine 18 extruding.After first medicine provided, batch pan 62 turned left, and so next duct 64 and medicine 18 wherein are positioned on the bucket 56.Press the button and can produce new air pressure after 58 and next medicine 18 is injected next patients, remaining later on medicine 18 can inject to some patients similarly successively.Batch pan can move by manual or known automated process.

All parts of this device can be made up of plastics, yet automaton should be made of metal rustless steel preferably.For hand gear, piston 36 can be made of metal, if but the cross section enough greatly also can be made of plastics.Because apparatus of the present invention need not stainless pin, so cheap even piston 36 is made also more common syringe-like device by rustless steel, the preparation of stainless pin needs very high accuracy.The end 22 of main bucket 10 is preferably made nose cone shape.Main bucket can be made by a monoblock.Between perhaps main bucket outer wall 50 and the central duct 16 also but hollow.Cover bucket 12 is preferably made by transparent material, can see piston boit from the outside like this, and determine the operating position of piston boit with vision.

One end of medicine 18 can be made into the shape of toothpick, can make medicine be easy to transdermal like this and enter hypodermic layer.As known, an end of toothpick has a point to become barrel portion backward.Medicine is a solid, yet needs only not broken its structural intergrity of maintenance when transdermal, and medicine both can be that solid also can be semi-solid.Have been found that on the y direction of medicine, should have 8Killipoise to pulverize the medicine hardness of power at least can.To child's administration the time,, also can use the less medicine of the power of pulverizing because its skin is grown up carefully.

The amount of carrier should be decided according to medicine and model of action thereof in the medicine 18.Total principle is that active component should account for about 50% at least in the medicine.As long as suitable medicine is arranged, it has enough hardness, and the dosage of Chinese medicine of the present invention can account for to 100%.Medicine can pass through conventional technology, as compression, and hot melt, or extruding is prepared from.Compression mainly is the process that comprises film-making, can prepare the pellet of a toothpick shape in this process.Hot melt then comprises and mixing and the fusion active component to also have carrier if necessary.The product that will melt is molded as the medicine of toothpick shape then.Extruding mainly is by with active component, and the words that need also have carrier and liquid mixing, form semisolid cream, and the cream of gained is pressed through the very little opening of a diameter and forms rhabodoid once more.The tip portion of pin sample can or be prepared from after the drying before semi-solid rhabodoid drying.The size of medicine 18 mostly is 2mm most for its barrel portion diameter, but should be preferably 0.25 to 0.5mm 0.2 to 0.8mm, and length is between 1mm to 3cm.Certainly how much relevant the size of medicine and used dosage and active component be shared in carrier.

The internal diameter in duct 16 should be than the diameter of medicine 18 big 5-10%.This can guarantee medicine by the time can " do not tangled " or looked like burr in rough and scrape damage by very tiny be not very slick duct 16 inner surfacies because might make aborning.The size that simultaneously also should limit diameter to be there to be certain CONTACT WITH FRICTION mutually, like this before the device administration medicine from the duct 16 because of the probability that drops out accidentally will be littler.Can also in the duct, add oil, can prevent on the one hand medicine from the duct because of dropping out accidentally, also can help the medicine transdermal on the other hand.

The diameter of medicine is not fixed, and having found to inject diameter is that 2mm or littler spicule can not cause pain.Certain larger-diameter medicine is not such situation, and larger-diameter medicine generally is by the sleeve pipe administration.

Active component can be peptide or protein, and the example of peptide class has growth hormone-releasing peptide (GHRP), luteinizing hormone releasing hormone (LHRH), somatostatin, the plain release peptide (GRP) of bombysin stomach, calcitonin, Kallidin I, lactotropin, melanocyte stimulates hormone (MSH), somatotropin releasing factor (GRF), amylopectin, tachykinin, secretin, parathyroid hormone (PTH), enkephalin, Endothelin, calcitonin-gene-related peptide (CGRP), neuromedin, parathyroid hormone-related protein (PTHrP), glucagon, neurotensin, thyroliberin (ACTH), peptide YY (PYY), Factor IX, vasoactive intestinal peptide (VIP), hypophysis adenosine cyclase activating peptide (PACAP), motilin, the P material, neuropeptide tyrosine (NPY), TSH and analog thereof and fragment.Other active component has insulin, epinephrine, lignocaine, morphine, glucocorticosteroid hormone (as dexamethasone), atropine, cell growth inhibited chemical compound, estrogen, androgen, interleukin, digitoxin, biotin, testosterone, heparin, ciclosporin, penicillin, vitamins, antiplatelet activity factor preparation (as ginkgolide), or stable.

In order to give active component at once, carrier should be water solublity.Water-solubility carrier has hyaluronic acid, cellulose such as hydroxypropyl emthylcellulose (HPMC), carbonyl methyl cellulose (CMC), hydroxyethyl-cellulose (HEC), poly-ethanol such as mannitol, saccharide such as dextrose, mannose, and glucose, gelatin, polyvinylpyrrolidone, and starch based.Carrier also can be water insoluble, but should be biodegradable, the administration that can continue like this.The example of suitable carrier has its water-fast polyesters such as L-lactic acid, D-lactic acid, DL-lactic acid, L-lactide, D-lactide, DL-lactide, Acetic acid, hydroxy-, bimol. cyclic ester, hydroxyacetic acid, decalactone (Capralactone), and any optical isomer, racemoid and copolymer thereof.

Below for illustrating administration of comparison solid dosage medicine and the administration of conventional liq dosage form, and to illustrate that two kinds of administering modes have similar pharmacological effect.

Example 1

Experimentize with biosynthetic human insulin (IHR) and ox pancreas insulin (IBP).IHR is pure water solublity insulin; IBP is an insulin zinc, and water insoluble and common glycerol with 16% is prepared from.Every milligram of IHR and IBP contain 26 insulin units approximately.

The insulin of more conventional injection type various dose.In the experiment of live body rat hypoglycemic effect, by the intensity and the speed of observation effect, all dosage forms are all effective.

Form with drying solid gives insulin, and its effect is identical basically with the non-gastrointestinal dosage form that is generally used for the pill injection.Needing few available device of the present invention as dose is the solid form cylinder medicine input patient of 0.45mm with the long diameter of 2mm.When with apparatus of the present invention the solid insulin being imported, patient is easy to operation and essentially no painful.The insulin chamber relaxing the bowels with purgatives of warm nature of this form can be stablized the long period, and liquid preparation that will be more common is cheap.

Example 2

The somatostatin analog, D-Nal-ring (Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2 is by (PVP is 5-10%) in conjunction with making an injectable tablet with dry matter gelatin and polyvinylpyrrolidone.Inject this tablet and with the conventional liq preparation difference of pharmacokinetics mode relatively.Result on the pharmacology of two kinds of method gained is actually identical.

Example 3

Synthetic anti--PAF, 4,7; 8,10-tetrahydrochysene-1-methyl-6-(2-chlorphenyl)-9-(4-anisyl-thiocarbamoyl)-pyrido-(4 ', 3 '-4; 5) thieno (3,2-f)-1,2; 4 ,-triazol (4,5-a) 1; the 4-diazepinone; and natural anti--PAF, ginkgolide B, the conventional administration of more above-mentioned two kinds of medicines.Because synthetic resisting-PAF does not dissolve, so routine is not used in parenteral introduction.But also find between pharmacological effect and blood concentration, to exist extraordinary dependency.Ginkgolide B is slightly soluble in water.Use the liquid dosage form (pH8.75) of same dosage, compare with solid drying agent, effect is identical in a period of time of injection beginning, yet liquid preparation can only continue 2 hours, and the effect of solid drying preparation can continue 24 hours.

Example 4

Prepare a long lasting decapeptide based formulation (month), use moulding machine that the shape of solid drugs is made diameter and be 0.8mm, length is several centimetres cylinder.

Use polylactide Acetic acid, hydroxy-, bimol. cyclic ester (PLGA, 80%), and this device is used for different types of animal (rabbit, Canis familiaris L., rat and pig), for implant or tiny balls, the pharmacokinetics of its control administration is identical, and solid preparation can well be through subcutaneous or intravenous administration.

The every clause that should be understood that claim is all changes and the modification that comprises the invention of applying for, its objective is to be used for illustrating marrow of the present invention and scope.

Claims (24)

1. One can parenteral introduction needleless device, this device is made up of bucket and piston, bucket has the first and second two ends, and the duct of a dressing solid dosage medicine, this duct is run through whole bucket from first end of bucket to second end, one bar is arranged on the piston, and its external diameter is identical with the internal diameter in duct.This piston rod is from second terminal the insertion in the duct of bucket, this piston can move in the duct and first end of medicine from bucket pushed out, if bucket is pressed on patient's the skin, and medicine has enough hardness to penetrate patient's skin, then can use this device that medicine footpath skin is injected patient.
2. 2. the device of claim 1 also can comprise a sleeve, and this sleeve combines with a piston, and this sleeve can slide on the outer surface of tube, and first and second ends are arranged on the sleeve.
3. 3. the device of claim 2 wherein has 2 rings to evagination prominent, and has an inwardly outstanding shoulder to dash forward on telescopic first end on the bucket, and the prominent sleeve that makes of this shoulder slides between two rings of tube are prominent.
4. 4. the device of claim 2, wherein piston includes a bar that is fixed on the distal end cap, and this distal end cap is combined on telescopic second end.
5. 5. the device of claim 4, wherein distal end cap by frictional engagement on telescopic second end.
6. 6. the device of claim 2 wherein also has one prominently from the second inwardly outstanding shoulder of this sleeve, and this shoulder is prominent to separate certain distance with first shoulder is prominent, and the prominent and main bucket of this second shoulder goes up that an outwards outstanding ring is prominent to combine mobile in main bunghole road of limited piston bar also.
7. 7. the device of claim 6, wherein the mobile of limited piston bar is to make piston rod not stretch out the main bucket first terminal 2mm of surpassing.
8. 8. the device of claim 6, wherein the mobile of limited piston bar is to make piston rod not exceed first end of main bucket at all.
9. 9. the device of claim 1, wherein first end of main bucket is the nose cone shape.
10. 10. the device of claim 1, it also has a medicine in the duct of main bucket.
11. 11. the device of claim 10, the profile of its Chinese medicine should be the shape of toothpick one end, promptly includes a tip, gradually becomes a cylinder backward, and its tip portion of the medicine in the duct is towards first end of main bucket.
12. 12. the device of claim 11, the diameter of its its barrel portion of Chinese medicine is about 0.2 to 2mm, and the total length of medicine is about 1mm to 5cm.
13. 13. the device of claim 10, the duct that wherein also has a plug of being made up of biocompatible material to seal main bucket first end is located.
14. 14. the device of claim 13, wherein biocompatible substances is mainly a class material that contains cellulose and gelatin.
15. 15. be suitable for the medicine to patient's parenteral introduction, its diameter is about 0.2 to 2mm, its length is about 1mm to 5cm, and such medicine should have enough hardness to penetrate patient's skin.
16. 16. the medicine of claim 15, this medicine contains 100% active component.
17. 17. the medicine of claim 15, the diameter of this medicine about 0.2 to 0.8mm.
18. 18. the medicine of claim 15, the diameter of this medicine about 0.25 to 0.50cm.
19. 19. the medicine of claim 15, the medicine hardness on long axis direction is at least about 8Killipoise.
20. 20. the medicine of claim 15, medicine are the toothpick shape, and are truncate epiconus at the one end.
21. 21. be suitable for the medicine of parenteral introduction, this medicine should contain 10% active ingredient at least, its diameter is about 0.2 to 2mm, and its length is about 1mm to 5cm, and the hardness of this medicine on long axis direction should be about 8Killipoise at least.
22. 22. the medicine in the claim 21, its diameter is about 0.2 to 0.8mm.
23. 23. need not to use pin to give the method for patient's parenteral introduction, this method comprises that the medicine that makes enough hardness can penetrate patient skin contacts with patient skin, and then extruding makes medicine pass patient's skin.
24. 24. can be through the non-needle device of non-stomach intestine medicine-feeding, this device is made up of bucket and feeder, this bucket has first and second ends, and the duct of running through whole bucket from first end to the second end of bucket, this duct is the medicine that is used for holding said solid form, feeder is by air drain, air-supplying valve and an action button are formed, depressing this action button can make gas enter in the said bucket through said valve from air drain, if this barrel is pressed on patient's the skin and depresses said button, if medicine has enough hardness can penetrate patient's skin simultaneously, like this, above-mentioned gas can be passed the medicine in the duct and it is pushed out the first terminal and penetrate patient's skin of bucket.

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