Drug delivery bullet

Abstract

The invention relates to a drug delivery bullet which comprises a drug delivery bullet head, and the drug delivery bullet head comprises a bullet head shell and a drug bullet body in a cavity of the bullet head shell. The bullet shell is a penetrable bullet shell, and the head part of the bullet shell is a locally thin part and is used for enabling a medicine bullet to penetrate through the head part of the bullet shell; or the bullet shell is a breakable bullet shell and is used for releasing the internal medicine pills when the bullet shell is impacted to deform and break; or, the bullet shell is a non-ruptured bullet shell, a bullet opening is formed in the bullet shell, the medicine bullet enters the living body along with the bullet shell, and the medicine is released in the living body through the bullet opening in the bullet shell; the medicine pill is a solid which carries medicine and can be dissolved or degraded in a living body. The invention has the beneficial effects that the medicine is carried into a living body through a dissolvable or degradable solid medicine pill and then is released, the leakage risk is small in the storage process, the activity of the medicine can be kept, and the high temperature and impact in the shooting process can be borne.

Description

Technical Field

[0001] The invention relates to the technical field of bullets, in particular to a drug delivery bullet. Background Art

[0002] In many dangerous situations, such as capturing fugitives, rescuing hostages, controlling riots or regional wars, traditional bullets can only effectively weaken the target's ability to move if they hit key parts of the body. Therefore, the use of such lethal weapons often results in serious casualties and consequences.

[0003] Drug-delivered bullets are proposed to maintain public order and safety while minimizing potential harm. Drug-delivered bullets can quickly and effectively weaken the target's ability to move by releasing drugs such as anesthetics wrapped in the bullet after hitting any area of ​​the body, and can control the target without causing serious life threats.

[0004] However, the current manufacturing process of drug-delivered bullets is very complicated, and it is difficult to maintain the activity of the drug during the manufacturing process. At the same time, the prepared drug-delivered bullets are also difficult to maintain the activity of the drug during long-term storage, and are difficult to withstand the high temperature and impact during the shooting process.

[0005] Dissolving microneedles (DMNs) are a new type of drug delivery system that can be developed for diseases such as diabetes, vaccination or cancer treatment. Dissolving microneedles are needle-shaped biopolymers with a uniform mixture of therapeutic agents inside. When the microneedles penetrate and dissolve in the skin, the therapeutic agents are released into the dermis. Summary of the invention

[0006] The technical problem to be solved by the present invention is that it is difficult for existing drug delivery bullets to maintain drug activity during storage and difficult to withstand high temperature and impact during shooting.

[0007] The technical solution adopted by the present invention to solve its technical problems is: a drug delivery bullet, comprising a drug delivery bullet, the drug delivery bullet comprising a bullet shell and a drug pellet in a cavity of the bullet shell; the bullet shell is a penetrable bullet shell, the head of the penetrable bullet shell is a locally thinner part, which is used to allow the drug pellet to penetrate the head of the bullet shell into a living body and release the drug after the drug delivery bullet hits the target; or, the bullet shell is a ruptured bullet shell, which is used to deform and rupture the bullet shell after the drug delivery bullet hits the target, release the internal drug pellet, and the drug pellet can continue to enter the living body to release the drug; or, the bullet shell is a non-ruptured bullet shell, which has a bullet opening on the bullet shell, which is used to allow the drug pellet to enter the living body together with the bullet shell after the drug delivery bullet hits the target and enters the living body, and release the drug in the living body through the bullet opening on the bullet shell; the drug pellet is a solid that can dissolve or degrade in the living body and carries the drug, and is used to release the carried drug.

[0008] It is further defined that the material of the drug pellet is soluble microneedle material.

[0009] It is further defined that the material of the drug pellet is a biodegradable material.

[0010] It is further specified that the material of the drug pellet is one or a combination of hyaluronic acid, silk fibroin, collagen, sodium carboxymethyl cellulose, alginate, chondroitin sulfate, polyvinyl pyrrolidone, cyclodextrin, polylactic acid, polyvinyl alcohol, polyacrylic acid, dextran, sucrose, maltose, fructose, chitosan, agarose, sorbitol, mannitol, and polyurethane.

[0011] It is further defined that the drug pellet carries the drug by mixing the drug into the material of the drug pellet; or, the drug pellet carries the drug by filling the drug into the cavity of the drug pellet.

[0012] It is further defined that the drug pellets are drug pellets compressed from drug powder.

[0013] It is further defined that the surface of the drug pellet has a pellet protection layer for protecting the internal drug pellet and breaking when subjected to a strong force to expose the internal drug pellet.

[0014] It is further defined that the bullet protection layer is a mineralized film or a polyimide film or a composite film thereof, or the bullet protection layer is a double-layer film composed of a mineralized film and a polyimide film or a composite film thereof, and the polyimide film or the composite film thereof is located in the outer layer.

[0015] It is further defined that the bullet shell includes a bullet shell body and a weighted base, the tail of the bullet shell body is fixed on the weighted base, and the tail of the bullet shell body is open, and the bullet shell body covers the medicinal projectile through the tail opening.

[0016] It is further defined that the material of the warhead shell body of the penetrable warhead shell is rubber; the material of the warhead shell body of the rupture type warhead shell is ceramic or glass; the material of the warhead shell body of the non-rupture type warhead shell is metal; and the material of the weighted base is lead.

[0017] It is further defined that the drug projectile is in the shape of a bullet, the tip of the drug projectile is arranged forward, and the tail of the drug projectile is fixed on the weight-increasing base.

[0018] It is further defined that the drug is one or a combination of poison, toxin, anesthetic, and virus.

[0019] It is further defined that the mineralized film is formed by surface cross-linking and mineralization reaction; the polyimide film or its composite film is specifically a photocurable polyimide film or a boron nitride / polyimide composite film.

[0020] It is further defined that the surface of the drug pellet has a mineralized film; or the entire drug pellet is completely mineralized.

[0021] The beneficial effects of the present invention are:

[0022] After hitting any area of ​​the body, the drug such as anesthetic in the drug-delivered bullet can be released to quickly and effectively weaken the target's ability to move, and the target can be controlled without causing serious life threats. This new drug-delivered bullet can be used by police law enforcement, the military or security groups to control targets in dangerous situations without deadly force.

[0023] The drug is carried into the body through soluble or degradable solid drug pellets and then released. There is a low risk of leakage during storage, the drug activity can be maintained, and it can withstand the high temperature and impact during the shooting process.

[0024] Placing the drug pellet in the bullet casing can better protect the drug pellet.

[0025] The drug pellets prepared by the soluble microneedle material can be made by a mold method, which has a simple process and is easy to operate, and the entire preparation process will not destroy the biological activity of the drug.

[0026] The mineralized film can enhance the mechanical strength of the drug pellets, better ensure that the drug pellets have sufficient mechanical strength to penetrate the skin, and protect the internal drug pellets from being lost.

[0027] The mineralized film is moisture-resistant and stable, and can also improve the biological activity of the drug pellets, extend the long-term storage of the drug pellets and maintain the drug activity during storage.

[0028] During the shooting process of drug bullets, high temperatures will be generated. The mineralized film can improve the heat resistance stability of drug bullets, avoid the reduction of mechanical strength of drug bullets under high temperatures during the shooting process, and reduce the activity of drugs.

[0029] The polyimide film or its composite film can enhance the waterproofness, high temperature resistance and toughness of the drug projectile. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The present invention is further described below in conjunction with the accompanying drawings and embodiments;

[0031] Figure 1 is a stereoscopic diagram of a penetrable drug delivery bullet according to Example 1 of the present invention;

[0032] Figure 2 1 is a schematic diagram of the front structure of a penetrable drug delivery bullet according to Example 1 of the present invention;

[0033] Figure 3 yes Figure 2 AA section view;

[0034] Figure 4 is a stereoscopic view of a drug delivery bullet with a transparent penetrable bullet shell according to Example 1 of the present invention;

[0035] Figure 5 is a perspective view of a rupturable drug delivery bullet according to Example 7 of the present invention;

[0036] Figure 6 1 is a schematic diagram of the front structure of a rupturable drug delivery bullet according to Example 7 of the present invention;

[0037] Figure 7 yes Figure 6 BB cross-section diagram;

[0038] Figure 8 is a perspective view of a drug delivery bullet with a see-through rupturable bullet shell according to Example 7 of the present invention;

[0039] Fig. 9 is a stereoscopic view of a non-rupture type drug delivery bullet of Example 8 of the present invention;

[0040] Fig.10 1 is a schematic diagram of the front structure of a non-rupture type drug delivery bullet according to Example 8 of the present invention;

[0041] Fig.11 yes Fig.10 CC profile of ;

[0042] Fig.12 is a stereoscopic view of a drug delivery bullet with a transparent non-fragmentation type bullet shell according to Example 8 of the present invention;

[0043] In the figure, 1. drug delivery bullet, 1-1. bullet shell body, 1-2. drug pellet, 1-3. weighted base, 2. locally thinner part, 3. bullet opening, 4. cartridge case, 5. propellant, 6. primer. DETAILED DESCRIPTION

[0044] Example 1

[0045] like Figures 1 to 4 As shown, a drug delivery bullet includes a drug delivery bullet 1, which includes a bullet shell and a drug pellet 1-2 in the cavity of the bullet shell. The drug delivery bullet also includes a cartridge case 4, a propellant 5 and a primer 6. The combination of the drug delivery bullet 1, the cartridge case 4, the propellant 5 and the primer 6 is the same as that of existing bullets.

[0046] The bullet shell is a penetrable bullet shell, and the head of the penetrable bullet shell is a locally thinner part, which is used to allow the drug pellets 1-2 to penetrate the head of the bullet shell and enter the biological body to release the drug after the drug delivery bullet 1 hits the target.

[0047] The drug pellet 1-2 is a solid that carries drugs and can be dissolved or degraded in the body, and is used to release the carried drugs. The surface of the drug pellet 1-2 has a pellet protection layer, which is used to protect the internal drug pellet 1-2 and ruptures when subjected to strong force to expose the internal drug pellet 1-2.

[0048] The material of the drug pellets 1-2 is a soluble microneedle material, which includes but is not limited to hyaluronic acid, silk fibroin, collagen, sodium carboxymethyl cellulose, alginate, chondroitin sulfate, polyvinyl pyrrolidone, cyclodextrin, polylactic acid, polyvinyl alcohol, polyacrylic acid, dextran, sucrose, maltose, fructose, chitosan, agarose, sorbitol, mannitol, and polyurethane. The material of the drug pellets 1-2 is one or a combination of several of these materials.

[0049] The drug pellet 1-2 carries the drug by mixing the drug into the material of the drug pellet 1-2; or, the drug pellet 1-2 carries the drug by filling the drug into the cavity of the drug pellet 1-2.

[0050] The bullet protection layer is a mineralized film.

[0051] The warhead shell includes a warhead shell body 1-1 and a weight-added base 1-3, the tail of the warhead shell body 1-1 is fixed on the weight-added base 1-3, and the tail of the warhead shell body 1-1 is open, and the warhead shell body 1-1 covers the medicinal projectile 1-2 through the tail opening.

[0052] The material of the warhead shell body 1-1 of the penetrable warhead shell can be rubber or other elastic polymer materials.

[0053] The material of the weighted base 1-3 can be lead, or other heavy metal materials.

[0054] The drug pellet 1-2 is in the shape of a bullet, the tip of the drug pellet 1-2 is set forward, and the tail of the drug pellet 1-2 is fixed on the weight-increasing base 1-3. Of course, it is not ruled out that the drug pellet 1-2 can be in other shapes, as long as it is ensured that the drug pellet 1-2 of this shape can penetrate the head of the penetrable bullet shell and enter the biological body such as the human body, such as a cone shape. The drug pellet 1-2 can be directly solidified on the weight-increasing base 1-3 to achieve the fixation of the drug pellet 1-2 and the weight-increasing base 1-3, or a protruding structure is set on the weight-increasing base 1-3 to clamp the solidified drug pellet 1-2, or the drug pellet 1-2 is bonded to the weight-increasing base 1-3 by a bonding material.

[0055] The tail of the dosing bullet 1 is mounted on the cartridge case 4, specifically, it is mounted on the cartridge case 4 via a weighted base 1-3.

[0056] Drugs include, but are not limited to, poisons, toxins, anesthetics, viruses, or a combination thereof. For example, peptide drugs, protein drugs, propofol, dimethoxyamphetamine (DMA), Lorazepam, Psilocin, Zopiclone, cyanide, nitrite, arsenic and its compounds, Tripterygium wilfordii, Datura, Lily of the Valley, strychnine, snake venom, bee venom, bromide, potassium permanganate, botulinum toxin, ricin, pathogenic bacteria and viruses, etc. Preferably, the drug is fast-acting and can quickly incapacitate the target.

[0057] The mineralized film is selected from at least one insoluble divalent inorganic salt, and can be formed by cross-linking and mineralization reaction. Specifically, the material of the drug pellets 1-2 is cross-linked with calcium ions, zinc ions, copper ions or silver ions to form a cross-linked composite gel with certain mechanical strength and toughness, and then immersed in a phosphate, carbonate, bicarbonate or chloride solution for mineralization reaction, and a layer of mineralized film is formed on the surface after drying.

[0058] Specifically, the present invention provides calcium ions, zinc ions, copper ions or silver ions through water-soluble divalent inorganic salts or their hydrates for cross-linking with the materials of the drug pellets 1-2. The water-soluble divalent inorganic salts include, but are not limited to, one or more of magnesium chloride, zinc chloride, calcium chloride, magnesium sulfate, zinc sulfate, calcium sulfate, magnesium nitrate, zinc nitrate, calcium nitrate, magnesium acetate, zinc acetate, and calcium acetate; wherein the magnesium chloride hydrate may be magnesium chloride hexahydrate, and the calcium chloride hydrate may be calcium chloride dihydrate.

[0059] The mineralized film formed by the mineralization reaction includes, but is not limited to, one of zinc phosphate, calcium phosphate, silver phosphate, copper phosphate, zinc carbonate, calcium carbonate, silver carbonate, copper carbonate, and silver chloride, or a combination thereof.

[0060] Next, two soluble microneedle materials, alginate and sodium carboxymethyl cellulose, were selected to prepare a bullet-shaped alginate / sodium carboxymethyl cellulose complex drug pellet 1-2 containing a calcium phosphate mineralized film.

[0061] The trial production process is as follows:

[0062] Sodium carboxymethyl cellulose (CMC), sodium alginate (SA) and powdered drugs were uniformly mixed in a weight ratio of 1:1:1, heated to 200°C and melted into liquid, injected into the drug pellet mold, and demolded after cooling and solidification. Then, 20% CaCl2O3 by mass was sprayed on the surface of the drug pellet 1-2. 2 The resulting composite gel was soaked in a 20% by mass sodium phosphate solution to form a mineralized surface, and dried at 47° C. for 3 hours to obtain drug pellets 1-2 with a mineralized film on the surface.

[0063] The drug pellets 1-2 prepared by the soluble microneedle material can be made by a mold method, which has a simple process and is easy to operate, and the entire preparation process will not destroy the biological activity of the drug.

[0064] The drug pellets 1-2 are solid at room temperature, have a low risk of leakage during storage, can maintain drug activity, and can withstand high temperatures and impacts during shooting.

[0065] The mineralized film can enhance the mechanical strength of the drug pellets 1-2, better ensure that the drug pellets 1-2 have sufficient mechanical strength to penetrate the skin, and protect the internal drug pellets 1-2 from being lost. Before mineralization, the mechanical strength of the drug pellets 1-2 without mineralization treatment in this embodiment 1 can fully penetrate the exposed skin. After mineralization treatment, the mechanical strength of the drug pellets 1-2 with the mineralized film can fully penetrate clothing and skin.

[0066] The mineralized film has moisture-resistant stability, and can also improve the biological activity of the drug pellets 1-2, extend the shelf life of the drug pellets 1-2, and maintain the drug activity during the storage process.

[0067] During the shooting process of the drug bullet, high temperature will be generated. The mineralized film can improve the heat resistance stability of the drug projectile 1-2 and reduce the risk of reduced mechanical strength of the drug projectile 1-2 and reduced activity of the drug under high temperature during the shooting process.

[0068] Design and preparation method of lead weighted base 1-3:

[0069] The dosing bullet 1 is installed on the cartridge case 4 through a weighted base 1-3 made of lead material. An annular groove is provided in the middle of the weighted base 1-3 to facilitate the installation and fixing of the hollow rubber bullet shell body 1-1.

[0070] During the preparation process, the lead material is melted and then shaped through a mold to form a weighted base 1-3, which is then assembled with the cartridge case 4 and the warhead shell body 1-1.

[0071] Design and preparation method of cartridge case 4:

[0072] The cartridge case 4 is a cartridge case 4 made by stamping and stretching. It needs to go through multiple stamping and stretching to gradually change from a copper plate to the shape of the cartridge case 4. The cartridge case 4 is the main carrier of the bullet. The bullet can be subdivided into parallel bullets, straight-barrel bullets, etc. The shape of the cartridge case 4 of the straight-barrel bullet is similar to a bucket, while the parallel bullet has a larger belly of the cartridge case 4 and becomes a water bottle shape under the premise of keeping the maximum diameter of the bullet head unchanged, so as to put more propellant 5. The disadvantage is that the geometric shape is complex and more difficult to process, so most of them are rifle bullets with a large amount of powder, while straight-barrel bullets are mostly pistol bullets with a small amount of powder.

[0073] During the preparation process, the brass sheet is first fed into the shear die-casting machine, and the die will press out a small brass cup. The manufactured brass cup base is cleaned, polished, and dried. It also undergoes quality inspection and size inspection, and the machine can quickly screen out brass cups that do not meet the specifications. Then, through the expansion and stretching of the machine, it becomes a cylinder with a thinner and more slender inner wall, forming a shell structure.

[0074] Design and preparation method of primer 6:

[0075] The primer 6 is located at the center of the bottom of the cartridge case 4. The primer 6 is ignited by the firing pin, and the flame is led to the chamber of the cartridge case 4 through the fire transfer hole, thereby completing the firing.

[0076] Bullet Assembly:

[0077] The assembly is performed by a machine, firstly a fixed amount of propellant 5 is loaded into the cartridge case 4, and then the dosing bullet 1 is assembled on the cartridge case 4.

[0078] The use process of the drug delivery bullet of this embodiment 1 is as follows:

[0079] After the drug delivery bullet is fired, the drug delivery bullet 1 is ejected and hits the target, and the drug pellet 1-2 in the drug delivery bullet 1 continues to move forward due to inertia, penetrates the bullet shell and pierces into a biological body such as a human body. In the process of the drug delivery bullet 1 hitting the target, the drug pellet 1-2 penetrating the bullet shell and piercing into the biological body, a strong impact will be generated, causing the drug pellet 1-2 to be subjected to a strong force, the mineralized film will rupture, and the tissue fluid in the human body will dissolve the drug pellet 1-2 through the rupture of the mineralized film to release the drug. The weighted base 1-3 and the rubber bullet shell fall off outside the body.

[0080] The drug pellet 1-2 is in the shape of a bullet, and the design that the tip of the drug pellet 1-2 is arranged forward can make it easier for the drug pellet 1-2 to penetrate the bullet shell and penetrate into the human body.

[0081] The weighted base 1-3 can increase the mass of the dosing bullet 1, increase the speed retention capability and stability. Since the mass of lead is greater than that of copper, the lead weighted base 1-3 allows the bullet to have greater kinetic energy, and the texture is softer, which can reduce the wear of the gun barrel.

[0082] Example 2

[0083] A drug delivery bullet is basically the same as Example 1, except that: the drug pellet 1-2 is an alginate / polyvinyl alcohol composite drug pellet containing a calcium phosphate mineralized film.

[0084] The trial production process is as follows:

[0085] Dissolve 2.5 g of polyvinyl alcohol (PVA) in 50 ml of water. Mix vigorously with 0.1 M HCl at 40 °C and adjust the pH of the solution to 4 for 4 hours. Finally, gradually add 5 g of sodium alginate and 5 g of the drug until a uniform paste is formed by stirring at room temperature. Immerse the paste in CaCl 2 (0.1M) and mixed vigorously for a period of time, after which the pH value was adjusted to 4. Sodium alginate is fully cross-linked with calcium ions, which further enhance the biological activity through the biomimetic process of in situ mineralization. Then, the formed mixed hydrogel solution was gently stirred with a solution rich in phosphorus ions at room temperature for 3 days until a calcium concentration of 0.24M and a phosphate concentration of 0.12M were reached. Finally, the composite mixture was gently stirred at room temperature for 7 days, then thoroughly washed three times in deionized water, added to the drug pellet mold, and dried to obtain alginate / polyvinyl alcohol composite drug pellets with a calcium phosphate mineralized film on the surface.

[0086] Example 3

[0087] A drug delivery bullet is basically the same as Example 1, except that: the drug pellet 1-2 is an alginate / hyaluronic acid composite drug pellet containing a calcium phosphate mineralized film.

[0088] The trial production process is as follows:

[0089] Prepare a 15% hyaluronic acid solution and an 8% sodium alginate solution. Mix the hyaluronic acid solution, sodium alginate solution and the anesthetic drug Lumianning in a 1:1:1 mass ratio, inject into the drug pellet mold, and dry at 45°C for 2h. After demolding, spray the surface with 20% CaCl 2 The resulting composite gel was soaked in a 20% trisodium phosphate solution to form a mineralized surface, and then dried at 47°C for 3 hours to obtain alginate / hyaluronic acid composite drug pellets containing a calcium phosphate mineralized film.

[0090] The role of hyaluronic acid is to provide toughness and increase the viscosity of the solution to speed up drying, while the role of sodium alginate is to cross-link with calcium ions to form a gel.

[0091] Example 4

[0092] A drug delivery bullet is basically the same as Example 1, except that: the drug pellet 1-2 is a collagen drug pellet containing a calcium phosphate mineralized film.

[0093] Mineralized collagen is a component of various connective tissues, such as bone, cartilage, tendon and dentin. Ordered, organized mineralized collagen with a unique nanostructure forms the basis of a range of physiological functions of connective tissue. The extracellular bone matrix contains 60% to 70% mineral components in the form of nanoapatite crystals, 20% to 30% collagen fibers and 10% to 20% water. The main components of this mineral are hydroxyapatite (HAP, Ca 10 (PO 4 ) 6 (OH) 2 ), with a stoichiometric calcium / phosphorus ratio of 1.67. In fact, HAP in natural bone tissue is usually calcium-deficient, with a Ca / P ratio lower than 1.67.

[0094] In the mineralization process of mineralized collagen, nucleation sites are crucial for the formation of mineral crystals. Previous studies have shown that negatively charged carboxyl groups (-COOH) exist in about 11% of the amino acid residues in collagen molecules, which are the main nucleation sites for the mineralization of collagen fibrils. 2+ ) on these carboxyl groups is a key factor in the initial step of crystal nucleation. Subsequent studies have shown that the carboxyl and carbonyl groups (C=O) on collagen are not only another nucleation site for HA crystal mineralization, but also the oxygen atoms of these two groups are closely related to Ca2+ Coordination, as the core of heterogeneous nucleation, then crystal nucleation and growth. Mineralized collagen fibers further aggregate to form a matrix with a three-dimensional network structure, which serves as a template for further mineralization. In mineralized collagen, the conformation of collagen changes, and collagen fibrils are connected by sugar hydroxyl groups and Ca 2+ The coordination bonds between the collagen are cross-linked, making the collagen insoluble in water. The assembly and organization of collagen provide intramolecular space for the nucleation and growth of HAP crystals.

[0095] Based on the above principles, the preparation of collagen drug pellets containing calcium phosphate mineralized film was implemented.

[0096] The trial production process is as follows:

[0097] Ca(OH) 2 , phosphoric acid and porcine collagen as starting materials, and synthesized collagen containing hydroxyapatite surface by simultaneous titration under controlled pH and temperature. Under the conditions of 40°C and pH=8, the drug pellet mold was injected to prepare collagen drug pellets containing calcium phosphate mineralized film. The drug pellets 1-2 have mechanical strength to pierce the skin and retain a certain toughness.

[0098] Example 5

[0099] A drug delivery bullet is basically the same as embodiments 1 to 4, except that: in order to enhance the waterproof, high temperature resistance and toughness of the drug pellets 1-2, a waterproof and fireproof bullet protection layer is coated on the surface of the drug pellets 1-2 containing the calcium phosphate mineralized film in embodiments 1 to 4. Only when subjected to a strong impact, the second bullet protection layer is broken like the mineralized film, and the drug pellets 1-2 inside can be dissolved to release the drug.

[0100] The second projectile protection layer is a polyimide film or a composite film thereof. The trial production process of the polyimide film or the composite film thereof is as follows:

[0101] Add 203g N-methylpyrrolidone (NMP) to a two-necked flask protected by N2, place it in an ice-water bath, add 7.61g (0.05mol) 3,5-diaminobenzoic acid (DABA); after complete dissolution, slowly add 22.88g (0.515mol) 4,4'-(hexafluoroisopropylene) diphthalic anhydride (6FDA) in batches, react for 10h, add 20mL toluene and 2mL triethylamine, stir evenly, move into an oil bath, heat to 110℃, react for 5h to remove water; heat to 200℃ and continue to react for 5h, The reaction solution was cooled to room temperature, and a clear solution of 10.66 g (0.075 mol) of glycidyl methacrylate (GMA), 0.32 g of triphenylphosphine (TPP) and 0.32 g of hydroquinone (HQ) was added. After stirring evenly, it was heated to 110°C for reaction for 10 hours. After cooling to room temperature, the reaction solution was poured into 2 L of anhydrous ethanol to precipitate the precipitate; it was washed alternately with 1 L of water and 1 L of anhydrous ethanol for 3 to 5 times, and vacuum dried at 45°C to obtain a photosensitive fluorinated polyimide oligomer (PSPI).

[0102] The photosensitive fluorinated polyimide oligomer, solvent N-vinyl pyrrolidone (NVP), active diluent hydroxyethyl acrylate (HEA) and polyethylene glycol diacrylate (PEG400DA), and photoinitiator IRGACURE 819 are ultrasonically uniformly mixed to prepare a photosensitive polyimide resin. The prepared drug pellets 1-2 containing a mineralized film are immersed in the prepared photosensitive polyimide resin to form a film on the surface of the drug pellets 1-2, and then placed in a UV curing box for exposure and curing, and finally vacuum dried at 25° C. for 1 hour to obtain a layer of photocured polyimide film on the surface of the drug pellets 1-2.

[0103] The mineralized film and polyimide film or their composite film used as the bullet protection layer can be broken when subjected to strong force by controlling the thickness of each film layer.

[0104] Example 6

[0105] A drug delivery bullet is basically the same as Example 5, except that the second bullet protection layer is a boron nitride / polyimide composite film.

[0106] The trial production process of this layer of boron nitride / polyimide composite film is as follows:

[0107] First, 1g of hexagonal boron nitride (h-BN), 30g of urea (mass ratio of 1:30) and 12ml of deionized water were weighed and added to a ball mill and filled with nitrogen. At room temperature, the mixture was placed in a planetary ball mill and ball milled at 500rpm for 20h. Subsequently, the mixture was diluted to 500ml and ultrasonically treated for 1 hour. After the ultrasonic treatment, the unpeeled h-BN was removed by centrifugation at 3000rpm for 15 minutes. The supernatant was further washed with deionized water for 5 times to remove residual urea. After drying at 65°C in an electric blast drying oven for 24h, boron nitride nanosheets (BNNS) were finally obtained. 6g of chopped PPTA fibers and 4gKOH were weighed and immersed in 500ml of dimethyl sulfoxide (DMSO) solution and sealed intact. After magnetic stirring at room temperature for one week, 8mg mL -1 Aramid nanofiber (ANFs) / DMSO dispersion. The mass ratio of added BNNS and ANFs was 1:1. First, a certain amount of BNNS (0.3, 0.5, 0.7 and 1.0wt%) was dispersed in dimethylacetamide solvent (DMAc) using an ultrasonic cleaner. Under mechanical stirring, a certain amount of ANFs / DMSO (0.3, 0.5, 0.7 and 1.0wt%) was slowly added at a rate of 6s / drop, and stirring was continued for 2h. Weigh 1g of diphenyl ether diamine (ODA) and add it to the above solution. Continue stirring until ODA is fully dissolved, then add 1.2g of pyromellitic dianhydride (PMDA) in batches, and continue stirring for 6h to prepare a pre-film solution. All the above operations were carried out at room temperature. The prepared pre-film solution was cast on the drug pellets 1-2 containing the mineralized film and placed in an oven for a thermal imidization process at 80℃ / 4h. Finally, take out the medicine pellets 1-2 and cool them naturally to obtain the second pellet protection layer.

[0108] Example 7

[0109] like Figures 5 to 8 As shown, a drug delivery bullet is basically the same as embodiments 1 to 6, except that the bullet shell is a ruptured bullet shell, which is used to deform and rupture when the bullet hits the target, releasing the internal drug pellets 1-2, and the drug pellets 1-2 can continue to enter the organism to release the drug.

[0110] The material of the warhead shell body 1-1 of the rupturable warhead shell is ceramic, and can also be glass.

[0111] The drug pellet 1-2 is also in the shape of a bullet, the tip of the drug pellet 1-2 is set forward, and the tail of the drug pellet 1-2 is fixed on the weight-increasing base 1-3. Of course, it is not excluded that the drug pellet 1-2 can be in other shapes, as long as the drug pellet 1-2 of the shape can penetrate into a biological body such as a human body.

[0112] After the drug delivery bullet of Example 7 is fired, the drug delivery bullet 1 is ejected and hits the target, and the ruptured bullet shell is ruptured. The drug pellets 1-2 in the drug delivery bullet 1 continue to move forward due to inertia and penetrate into a living body such as a human body. In the process of the drug delivery bullet 1 hitting the target and penetrating the living body, a strong impact is generated, causing the drug pellets 1-2 to be subjected to a strong force, and the bullet protective layer is ruptured. The tissue fluid in the human body dissolves the drug pellets 1-2 through the rupture of the bullet protective layer, and releases the drug. The weighted base 1-3 and the bullet shell made of ceramic material fall off outside the body.

[0113] Example 8

[0114] like Figures 9 to 12 As shown, a drug delivery bullet is basically the same as embodiments 1 to 6, except that the bullet shell is a non-rupture bullet shell, and has a bullet opening 3 on the bullet shell, so that after the bullet hits the target and enters the organism, the drug bullet enters the organism together with the bullet shell, and releases the drug in the organism through the bullet opening 3 on the bullet shell.

[0115] Specifically, the material of the warhead shell body 1-1 of the non-fragmentation type warhead shell is metal. The warhead opening 3 on the warhead shell is located on the side of the warhead shell.

[0116] The drug pellet 1-2 is also in the shape of a bullet, the tip of the drug pellet 1-2 is set forward, and the tail of the drug pellet 1-2 is fixed on the weight-added base 1-3. In this embodiment, because the drug pellet 1-2 does not need to have a penetrating property, the shape of the drug pellet 1-2 is not limited. For example, the shape of the drug pellet 1-2 is changed to a round shape, and fills the entire inner cavity of the bullet shell.

[0117] The penetrating power of the drug delivery bullet 1 of this embodiment is comparable to that of an ordinary metal bullet, and can not only penetrate thicker clothing and skin, but can even penetrate materials such as wooden boards.

[0118] After the drug delivery bullet 1 is fired and hits the target, even if the bullet shell is deformed, it cannot be guaranteed that it will rupture. The drug delivery bullet 1 is completely inserted into a biological body such as a human body. In the process of the drug delivery bullet 1 hitting the target and piercing the biological body, a strong impact will be generated, causing the internal drug pellets 1-2 to be subjected to a strong force, and the bullet protective layer will rupture. The tissue fluid in the human body enters the inner cavity of the bullet shell through the bullet opening 3 on the bullet shell, and the drug pellets 1-2 are dissolved through the rupture of the bullet protective layer to release the drug. The released drug then enters the human body through the bullet opening 3 on the bullet shell.

[0119] Example 9

[0120] A drug delivery bullet is basically the same as Example 1, except that the mineralized film such as calcium phosphate is a biomineral sensitive to pH value and can dissolve spontaneously under acidic conditions, but the dissolution rate is slower than that of the soluble microneedle material, and can play a sustained release role.

[0121] In the case where rapid release of the drug is not required, the thickness of the mineralized film can be increased, and the drug pellet 1-2 entering the human body does not need the mineralized film to break. The entire drug pellet 1-2 can even be completely mineralized.

[0122] The warhead casing may be a penetrable warhead casing, a rupturing warhead casing or a non-rupturing warhead casing.

[0123] The outer surface of the thickened mineralized film or the fully mineralized drug pellet 1-2 may or may not have a polyimide film or a composite film thereof as a pellet protection layer to enhance the waterproof, high temperature resistance and toughness of the drug pellet. The polyimide film or the composite film thereof needs to be broken when subjected to a strong force to expose the drug pellet 1-2 inside.

[0124] Example 10

[0125] A drug delivery bullet is basically the same as Example 1, except that: the surface of the prepared drug pellet 1-2 is not mineralized, and a layer of waterproof and fireproof polyimide film or its composite film is directly coated on the surface of the drug pellet 1-2 as a pellet protection layer.

[0126] The warhead casing may be a penetrable warhead casing, a rupturing warhead casing or a non-rupturing warhead casing.

[0127] Embodiment 11

[0128] A drug delivery bullet is basically the same as Example 1, except that the drug pellet 1-2 is a drug pellet 1-2 compressed from drug powder. The drug powder can be directly compressed into a solid drug pellet 1-2 of a desired shape under high pressure. For example, a tablet is a flaky solid compressed from drug powder by a tableting process. The drug powder is compressed into the drug pellet 1-2 using the tableting process of the tablet. In order to ensure that the performance of the drug pellet 1-2 meets the requirements such as mechanical strength, so that it can penetrate clothing and skin, additives can be added to the drug powder compressed into the drug pellet 1-2. The specific additives can be selected from the pharmaceutical additives for tablets, including fillers, wetting agents, adhesives, disintegrants, lubricants, etc.

[0129] The following is a specific formula of a drug pellet 1-2 made from compressed drug powder.

[0130] 9.6g of active drug, 30g of lactose, 10g of sodium carboxymethyl starch (DST), 30g of hydroxypropyl methylcellulose (HPMC), 60g of ethyl cellulose (EC), 8g of microcrystalline cellulose (MCC), about 50g of acrylic resin, an appropriate amount of 70% ethanol, and a small amount of magnesium stearate are added and mixed. The mixed powder is compressed into 1-2 drug pellets through a tableting process.

[0131] The surface of the drug pellet 1-2 compressed from the drug powder can also be coated with a pellet protection layer, which breaks when subjected to a strong force, exposing the drug pellet 1-2 inside. For example, a waterproof and fireproof polyimide film or a composite film thereof is coated on the surface of the drug pellet 1-2 as a pellet protection layer. The pellet protection layer breaks when subjected to a strong force, exposing the drug pellet 1-2 inside.

[0132] The warhead casing may be a penetrable warhead casing, a rupturing warhead casing or a non-rupturing warhead casing.

[0133] Example 12

[0134] A drug delivery bullet is basically the same as Example 1, except that the material of the drug bullet 1-2 is a biodegradable material. Polyimide or its composite material is a biodegradable material, which can be biodegraded in a living body such as a human body and slowly releases the drug. Because polyimide or its composite material has good waterproof, high temperature resistance and toughness, no additional bullet protection layer is required. The biodegradable material can also be polytetrafluoroethylene or its composite material.

[0135] The drug pellet (1-2) made of biodegradable material carries the drug by mixing the drug into the material of the drug pellet (1-2); or, the drug pellet (1-2) carries the drug by filling the drug into the cavity of the drug pellet (1-2).

[0136] The polyimide or its composite material and the polytetrafluoroethylene or its composite material are preferably carried by filling the drug into the cavity of the drug bullet (1-2).

[0137] The above-mentioned embodiments 1 to 12 are preferred embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solutions and inventive concepts of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A drug delivery bullet, comprising a drug delivery bullet (1), characterized in that: The drug delivery bullet (1) comprises a bullet shell and a drug pellet (1-2) in a cavity of the bullet shell; The warhead shell is a penetrable warhead shell, and the head of the penetrable warhead shell is a locally thinner portion (2), which is used to allow the drug pellets (1-2) to penetrate the head of the warhead shell and enter the biological body after the drug delivery warhead (1) hits the target, thereby releasing the drug; Alternatively, the bullet shell is a ruptured bullet shell, which is used to deform and rupture after the drug delivery bullet (1) hits the target, thereby releasing the drug pellet (1-2) inside, and the drug pellet (1-2) can continue to enter the body of the organism to release the drug; Alternatively, the bullet shell is a non-rupture type bullet shell, and has a bullet opening (3) on the bullet shell, so that after the drug delivery bullet (1) hits the target and enters the organism, the drug pellets (1-2) enter the organism together with the bullet shell, and release the drug in the organism through the bullet opening (3) on the bullet shell; The drug pellet (1-2) is a solid that carries drugs and can be dissolved or degraded in a living body, and is used to release the carried drugs.

2. The drug delivery bullet according to claim 1, characterized in that: The material of the drug pellets (1-2) is soluble microneedle material.

3. The drug delivery bullet according to claim 1, characterized in that: The material of the drug pellets (1-2) is biodegradable material.

4. The drug delivery bullet according to claim 1, characterized in that: The material of the drug pellets (1-2) is one or a combination of hyaluronic acid, silk fibroin, collagen, sodium carboxymethyl cellulose, alginate, chondroitin sulfate, polyvinyl pyrrolidone, cyclodextrin, polylactic acid, polyvinyl alcohol, polyacrylic acid, dextran, sucrose, maltose, fructose, chitosan, agarose, sorbitol, mannitol, and polyurethane.

5. The drug delivery bullet according to any one of claims 1 to 4, characterized in that: The drug pellets (1-2) carry the drug by mixing the drug into the material of the drug pellets (1-2); Alternatively, the drug pellet (1-2) carries the drug by filling the drug into the cavity of the drug pellet (1-2).

6. The drug delivery bullet according to claim 1, characterized in that: The drug pellets (1-2) are drug pellets (1-2) formed by compressing drug powder.

7. The drug delivery bullet according to claim 1, 2, 3, 4 or 6, characterized in that: The surface of the drug pellet (1-2) is provided with a pellet protection layer for protecting the drug pellet (1-2) inside, and is broken when subjected to a strong force, exposing the drug pellet (1-2) inside.

8. The drug delivery bullet according to claim 7, characterized in that: The warhead protection layer is a mineralized film or a polyimide film or a composite film thereof, or the warhead protection layer is a double-layer film composed of a mineralized film and a polyimide film or a composite film thereof, and the polyimide film or the composite film thereof is located in the outer layer.

9. The drug delivery bullet according to claim 1, characterized in that: The bullet shell comprises a bullet shell body (1-1) and a weight-added base (1-3); the tail of the bullet shell body (1-1) is fixed on the weight-added base (1-3); the tail of the bullet shell body (1-1) is open; the bullet shell body (1-1) covers the medicine projectile (1-2) through the tail opening.

10. The drug delivery bullet according to claim 9, characterized in that: The material of the warhead shell body (1-1) of the penetrable warhead shell is rubber; The material of the warhead casing body (1-1) of the rupturable warhead casing is ceramic or glass; The material of the warhead casing body (1-1) of the non-fragmentation type warhead casing is metal; The material of the weighted base (1-3) is lead.

11. The drug delivery bullet according to claim 9, characterized in that: The drug pellet (1-2) is in the shape of a bullet, the tip of the drug pellet (1-2) is arranged forward, and the tail of the drug pellet (1-2) is fixed on the weight-increasing base (1-3).

12. The drug delivery bullet according to claim 1, characterized in that: The medicine is one or a combination of poison, toxin, anesthetic and virus.

13. The drug delivery bullet according to claim 7, characterized in that: The mineralized film is formed by surface cross-linking and mineralization reaction; The polyimide film or its composite film is specifically a photocurable polyimide film or a boron nitride / polyimide composite film.

14. The drug delivery bullet according to claim 1, 2, 3 or 4, characterized in that: The surface of the drug pellet (1-2) has a mineralized film; or the entire drug pellet (1-2) is completely mineralized.

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