| Powder Needless Injector is a novel drug delivery device, which uses supersonic airflow produced by gas expansion under high pressure to energize drug powders to penetrate the stratum corneum into dermis or subcutaneous tissue. It represents attractive advantages in many aspects such as no needles, no pain, no cross-infection, convenience and efficiency. It is suitable for children, needle-feared patients and patients with chronic diseases requiring long-term administration, furthermore, especially for medical and preventive health care under conditions of major events (war, earthquake, flood, fulminating infectious disease), remote areas and large-scale field operation. Based on the preliminary studies, our group tries to develop an automatic powder needless (single) injector and synthetically evaluate its performance. The main results are as follows:1. Firstly developed a self designed prototype of solo-dose automatic powder needleless injector:Aimed at overcoming defects that preliminary powder needless injector cannot accomplish automation, this study made use of the advantages of military industrial technology in our country, firstly developed a powder needless (single) injector with totally new structure (Patent Application No.201010153045.4) and processed 3 prototypes. This device used new structure of torsional spring activated ball valve to achieve automatic delivery, and the drive was portable and could accomplish instantaneous delivery. In addition, it had advantages of good repeatability and high reliability, and also effectively avoided foreign patents. The device used design of high throughput to improve the delivery efficiency; ball valve with high air tightness to extend the storage period; reusable structure to reduce the cost; multi-joint reducer muffler to reduce injection squealing sound; replaceable interval enclosures to adjust injection parameters; special safety lock device to avoid false percussion and ensure the security; and non-slip handle design and sunken slotted airvent design to possess the characteristics of beautiful appearance, compact structure, according with ergonomics and fitting for single one-handed operation.2. Systematically investigated the mechanical reliability of self-made prototype:To assess the reliability and environmental requirements of self-made prototype, tolerated pressure, low temperature, high temperature, water immersion, drop test, fatigue test of the device and operation effects of different groups were tested, and the results revealed: self-made prototype was still safe at lOMPa when aerated and had no leakage; it did not affect the operation of mechanical structure whether under ambient temperature from-40℃to 60℃or fallen into water; It was still undamaged when dropped from the height of 75cm; there was no instrumental fatigue phenomenon after 48 times'continuous administration; the operation was effective among groups of different sexes and ages (18-60 years).3. Investigated and determined the safe operation conditions of self-made prototype: the skin injury and its influencing factors of self-made prototype were investigated through orthogonal test. The influencing factors of skin injury of prototype were as follows:injection pressure> cylinder capacity> injection distance> acceleration length; Combined with theoretical calculation and numerical simulation, the aerodynamic parameters and mechanisms of the main factors were determined; According to the requirements of totally no visible damage of skin, the interval of consecutive injections at the same site should be longer than 24h, and the interval of administration at alternate sites should be longer than 12h.4. Insulin was selected as a model drug to evaluate the effects of drug delivery by self-made prototype:Alloxan induced diabetic rabbits were selected as model to evaluate the antidiabetic effects of insulin powder needless injector which carrier was various salts. Compared with the subcutaneous injection by conventional needles, relative bioavailability (FR) was calculated through blood glucose area above the curve (AAC) and the results showed that:1) all of the insulin powder needless injectors which carrier was various salts had hypoglycemic effects, while insulin powder needless injector had almost no hypoglycemic effect. Therefore, it suggested that carrier material had greater impact on the effects of powder needless injector.2) under the same preparation conditions, the effects of the group which carrier was calcium carbonate was relatively poor and its FR was only 16.9±4.5%, while the FR of the group which carrier was phosphate was relatively high (38.6±8.2%).3) the insulin-phosphate powder was dissolved with saline and then conducted subcutaneous injection, FR was 44.7±9.6%, and it suggested that the actual effect of insulin-phosphate powder delivery by self-made powder needless injector was 70%, meanwhile, the activity loss of present relatively extensive pulverization of insulin was larger, which needed further optimization and improvement; 4) the hypoglycemic effects of insulin- phosphate powder delivery by powder needless injector in different sites of rabbits (thigh, buttock, back and abdomen) were compared, and the results revealed that the differences of FR and AAC among different sites were not significant, therefore, the effects of administration in different sites had no significant differences.5. The tetanus vaccine was selected as a model drug to evaluate the immune effects of vaccine delivery by self-made prototype:the tetanus IgG concentration in serum of guinea pig was selected as an index to evaluate the immune effects of automatic powder needless injector. The results revealed that:1) IgG concentrations in guinea pig serum of powder needless injector group with different doses showed significant dose-dependence; 2) 3,6,9 weeks after inoculation, IgG concentrations in guinea pig serum of powder needless injector group with same doses were similar to that of conventional needle injection group, there was no significant difference between them; 3) this study firstly evaluated the immunological enhancement of traditional Chinese medicine adjuvants combined with powder needless injector, and the results suggested that TCM adjuvants could assist vaccine pulverization and increase the IgG concentration in serum by tetanus vaccine powder needless injector. Among the TCM adjuvants, ginseng polysaccharide adjuvants were best. Its IgG concentration in serum increased 29.75% compared with the group without adjuvants after 9 weeks inoculation, and there were significant differences between the two groups. This study was first reported at home and abroad, and had applied for Chinese Patent (Application No.201110063283.0) and PCT (Application No. PCT/CN2011/072544).In summary, the novel automatic Powder Needless Injector has many advantages including easy operation, attractiveness and durableness, safety and reliability, and efficient administration. It can be used for not only therapeutic drug but also'preventative medicine, and has broad prospect of development and application. |
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