Conventional Subcutaneous Injection Research Articles

A Stereolithography-Based Modified Spin-Casting Method for Faster Laboratory-Scale Production of Dexamethasone-Containing Dissolving Microneedle Arrays

Microneedle arrays (MNAs) consist of a few dozens of submillimeter needles, which tend to penetrate through the stratum corneum layer of the skin and deliver hardly penetrating drugs to the systemic circulation. The application of this smart dosage form shows several advantages, such as simple use and negligible pain caused by needle punctures compared to conventional subcutaneous injections. Dissolving MNAs (DMNAs) represent a promising form of cutaneous drug delivery due to their high drug content, biocompatibility, and ease of use. Although different technologies are suitable to produce microneedle arrays (e.g., micromilling, chemical etching, laser ablation etc.), many of these are expensive or hardly accessible. Following the exponential growth of the 3D-printing industry in the last decade, high-resolution desktop printers became accessible for researchers to easily and cost-effectively design and produce microstructures, including MNAs. In this work, a low force stereolithography (LFS) 3D-printer was used to develop the dimensionally correct MNA masters for the spin-casting method. The present study aimed to develop and characterize drug-loaded DMNAs using a two-level, full factorial design for three factors focusing on the optimization of DMNA production and adequate drug content. For the preparation of DMNAs, carboxymethylcellulose and trehalose were used in certain amounts as matrices for dexamethasone sodium phosphate (DEX). Investigation of the produced DexDMNAs included mechanical analysis via texture analyzer and optical microscopy, determination of drug content and distribution with HPLC and Raman microscopy, dissolution studies via HPLC, and ex vivo qualitative permeation studies by Raman mapping. It can be concluded that a DEX-containing, mechanically stable, biodegradable DexDMNA system was successfully developed in two dosage strengths, of which both efficiently delivered the drug to the lower layers (dermis) of human skin. Moreover, the ex vivo skin penetration results support that the application of DMNAs for cutaneous drug delivery can be more effective than that of a conventional dermal gel.

Dual-Barb Microneedle with JAK/STAT Inhibitor-Loaded Nanovesicles Encapsulation for Tendinopathy.

Tendon stem/progenitor cells (TSPCs) are crucial for tendon repair, regeneration, and homeostasis. Dysfunction of TSPCs, due to aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, contributes to tendinopathy. Unfortunately, the effectiveness of conventional subcutaneous injection targeting at suppressing JAK/STAT signaling pathway is limited due to the passive diffusion of drugs away from the injury site. Herein, a novel poly-gamma-glutamic acid (γ-PGA) dual-barb microneedle (MN) path loaded with TSPCs-derived nanovesicles (NVs) containing JAK/STAT inhibitor WP1066 (MN-WP1066-NVs) for tendinopathy treatment is designed. The dual-barb design of the MN ensures firm adhesion to the skin, allowing for sustained and prolonged release of WP1066-NVs, facilitating enhanced TSPCs self-renewal, migration, and stemness in tendinopathy. In vitro and in vivo experiments demonstrate that the degradation of γ-PGA patch tips facilitates the gradual release of WP1066-NVs at the lesion site. This release alleviates inflammation, suppresses extracellular matrix degradation, and restores normal tendon histological structure by inhibiting the JAK/STAT pathway. These findings suggest that the multifunctional dual-barb MN patch offers a novel and effective therapeutic strategy for tendinopathy treatment.

Accelerated absorption of regular insulin administered via a vascularizing permeable microchamber implanted subcutaneously in diabetic Rattus norvegicus.

In Type 1 diabetes patients, even ultra-rapid acting insulins injected subcutaneously reach peak concentrations in 45 minutes or longer. The lag time between dosing and peak concentration, as well as intra- and inter-subject variability, render prandial glucose control and dose consistency difficult. We postulated that insulin absorption from subcutaneously implantable vascularizing microchambers would be significantly faster than conventional subcutaneous injection. Male athymic nude R. norvegicus rendered diabetic with streptozotocin were implanted with vascularizing microchambers (single chamber; 1.5 cm2 surface area per side; nominal volume, 22.5 μl). Plasma insulin was assayed after a single dose (1.5 U/kg) of diluted insulin human (Humulin®R U-100), injected subcutaneously or via microchamber. Microchambers were also implanted in additional animals and retrieved at intervals for histologic assessment of vascularity. Following conventional subcutaneous injection, the mean peak insulin concentration was 22.7 (SD 14.2) minutes. By contrast, when identical doses of insulin were injected via subcutaneous microchamber 28 days after implantation, the mean peak insulin time was shortened to 7.50 (SD 4.52) minutes. Peak insulin concentrations were similar by either route; however, inter-subject variability was reduced when insulin was administered via microchamber. Histologic examination of tissue surrounding microchambers showed mature vascularization on days 21 and 40 post-implantation. Implantable vascularizing microchambers of similar design may prove clinically useful for insulin dosing, either intermittently by needle, or continuously by pump including in "closed loop" systems, such as the artificial pancreas.

Implantable device with magnetically rotating disk for needle-free administrations of emergency drug.

Prompt administration of first-aid drugs can save lives during medical emergencies such as anaphylaxis and hypoglycemia. However, this is often performed by needle self-injection, which is not easy for patients under emergency conditions. Therefore, we propose an implantable device capable of on-demand administration of first-aid drugs (i.e., the implantable device with a magnetically rotating disk [iMRD]), such as epinephrine and glucagon, via a noninvasive simple application of the magnet from the outside skin (i.e., the external magnet). The iMRD contained a disk embedded with a magnet, as well as multiple drug reservoirs that were sealed with a membrane, which was designed to rotate at a precise angle only when the external magnet was applied. During this rotation, the membrane on a designated single-drug reservoir was aligned and torn to expose the drug to the outside. When implanted in living animals, the iMRD, actuated by an external magnet, delivers epinephrine and glucagon, similar to conventional subcutaneous needle injections.

Intradermal delivery of mRNA using cryomicroneedles

Microneedles can realize the intradermal and transdermal delivery of drugs. However, most conventional microneedles made of metal, polymer and ceramics are unsuitable for the delivery of mRNA drugs that are fragile and temperature-sensitive. This study explores the usage of cryomicroneedles (CryoMNs) for the intradermal delivery of mRNA molecules. Taking luciferase mRNA as an example, we first optimize the formulation of CryoMNs to maximize mRNA stability. Later, in the mouse model, we compare the delivery efficiency with the conventional subcutaneous injection for both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully induce specific B-cell antibody, neutralizing activity and T-cell responses. Statement of SignificancemRNA vaccines are fragile and temperature-sensitive, so they are mainly delivered by intramuscular injection that often causes pain and requires clinical expertise to immunize patients. Microneedles permit convenient, fast and safe vaccination. However, existing microneedle platforms are ineffective to protect the integrity of mRNA vaccines in fabrication, storage, and administration. This work utilizes cryomicroneedles (CryoMNs) technology to intradermally deliver mRNA. In the mouse model, CryoMNs are compared with the subcutaneous injection for the delivery efficiency of both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully produce specific B-cell antibodies, T-cell responses, and neutralizing activity. This work is expected to provide a new delivery strategy for the emerging mRNA therapeutics.

Immunogenicity of varicella-zoster virus vaccine by different routes of administration: Comparable vaccination efficacy of one-fifth dose intradermal vaccination to conventional subcutaneous vaccination

BackgroundThe live attenuated varicella-zoster virus (VZV) vaccine is used for the prevention of chickenpox and herpes zoster; however, there have been few studies on the immunogenicity of intradermal vaccination. ObjectiveTo compare the immunogenicity between subcutaneous and intradermal VZV vaccination. MethodsThirty healthy participants aged 50–75 who developed erythema less than 10 mm in diameter in VZV skin test were examined. Thirteen participants received full dose of VZV vaccine subcutaneously and 17 participants received one-fifth dose of vaccine intradermally. Immunogenicity to VZV was determined by VZV skin test reaction, proliferation of VZV-specific memory T cells, levels of VZV-specific serum antibody, and cytokine production from peripheral blood cells. ResultsVZV skin test reaction was similar between two groups. VZV-specific memory T cells were significantly increased only in the intradermal injection group. The increase of VZV-specific memory T cells correlated with Th1, Th2 and Th17 cytokines and cytotoxic molecules. No serious adverse events were observed in either group after vaccination. ConclusionIntradermal injection with one-fifth dose VZV vaccine showed a similar or greater effect on VZV-specific cellular immunostimulation than conventional subcutaneous injection. These findings suggest that one-fifth dose intradermal vaccination may have a comparable preventive effect to conventional subcutaneous injection.

Magnetically actuating implantable pump for the on-demand and needle-free administration of human growth hormone

A bolus of human growth hormone (hGH) is often prescribed for the treatment of growth hormone deficiency, which requires frequent injections in current clinical settings. This painful needle-involved delivery often results in poor patient compliance, leading to low medication adherence and poor clinical outcomes. Therefore, we propose a magnetically actuating implantable pump (MAP) that can infuse an accurate dose of hGH only at the time of non-invasive magnet application from the skin. The MAP herein could reproducibly infuse 20.6 ± 0.9 μg hGH per actuation without any leak at times without actuation. The infused amount increased proportionally with an increase in the number of actuations. When the MAP was implanted and actuated with a magnet in animals with growth hormone deficiency for 21 days, the profiles of plasma hGH concentration and insulin-like growth factor (IGF)-1, as well as changes in body weight, were similar to those observed in animals treated with conventional subcutaneous hGH injections. Therefore, we anticipate that the MAP fabricated in this study can be a non-invasive alternative to administer hGH without repeated and frequent needle injections.

Feasibility of chitosan-based nanoparticles approach for intranasal immunisation of live attenuated Japanese encephalitis vaccine

Intranasal (IN) administration, a non-invasive route, is explored to overcome the limitations of conventional subcutaneous (SC) injection for Japanese encephalitis (JE) immunisation. Mucoadhesive nanoparticles (NPs) are recognised for the benefits they offer via IN delivery, such as extended retention time of the vaccine on the mucosa. The purpose of this study was to evaluate immunisation effect of live attenuated Japanese encephalitis-chimeric virus vaccine (JE-CV)-loaded mucoadhesive NPs based on chitosan (CS) or chitosan maleimide (CM), a novel mucoadhesive polymer, via the IN route to improve the mucosal immunisation against JE. The results revealed that IN immunisation stimulated seroprotection following PRNT50 evaluation. Moreover, compared with SC immunisation, IN immunisation in mice provided a higher sIgA level, leading to improved mucosal immune response. In addition, chitosan-based NPs showed an adjuvant effect on the IN vaccine due to their mucoadhesive and antigen-uptaken properties. CM NPs successfully induced sIgA. In contrast, SC JE-CV immunisation induced negligible mucosal immunity. These immunological advantages revealed that JE-CV-loaded mucoadhesive NPs are a promising approach for IN vaccination as an alternative route for JE protection due to the stimulatory effects on both mucosal and systemic immune responses.

Magnetically-driven implantable pump for on-demand bolus infusion of short-acting glucagon-like peptide-1 receptor agonist

For type 2 diabetic patients, short acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) is often prescribed with frequent needled injections. Long-acting GLP-1 RA for less frequent injections do not mimic physiologic secretion of GLP-1. Therefore, an implantable pump is proposed in this work, which can deliver a short-acting GLP-1 RA, exenatide, without needles and batteries. The implanted pump can infuse an accurate amount of exenatide bolus only when a noninvasive magnetic force is applied from outside the body. The pump includes a safety feature of patterned magnets for actuation to prevent accidental infusion possibly caused by a general household magnet. The reservoir for exenatide is made of a flexible biomaterial and thus, a negative pressure build-up in the reservoir can be prevented even after multiple actuations and almost all drug consumption (~ 94%). This allows a reproducible drug dose for a longer period after implantation, hence less frequent replenishment procedures. The pump is also equipped with an intermediate container with two distinct check-valves and thus, the reservoir of exenatide can be further separated and better prevented from infiltration of the bodily fluid surrounding the implanted pump. When tested in Goto-Kakizaki rats, the pump demonstrates the efficacy of exenatide similar to conventional subcutaneous injections. Therefore, the pump can be promising for patient-friendly, optimal delivery of short-acting GLP-1 RA that better follows the physiologic secretion profile of GLP-1.

Development of an Immune Regulation Technology Targeting the Skin and Promotion of the Practical Applications of Transcutaneous Vaccination/Immunotherapy

In the premise of vaccination and allergen-specific immunotherapy, transcutaneous formulations have an advantage over conventional subcutaneous injections in terms of convenience, simplicity of delivery, and painless administration into the skin. Additionally, since transcutaneous formulations can be rendered cold-chain free, they do not require expert handling during transportation, storage, and stockpiling, which enables reductions in costs and distribution to distant areas. Furthermore, transcutaneous formulations are effective for improving adherence in children with phobias toward injection needles and may help in persuading them to perform self-vaccination and home immunotherapy against allergies in the future. We have been promoting the development of innovative "patch-type formulations for vaccination and immunotherapy" which regard skin as an immune organ and utilize our original transcutaneous administration devices (hydrophilic gel patch and microneedle patch) for their delivery. We have confirmed the safety and efficacy of transcutaneous formulations not only in demonstration experiments using animals but also in physician-initiated clinical studies. Additionally, in order to elucidate the mechanism for the induction of immune responses by transcutaneous formulations, we analyzed the immunological events occurring in the skin and regional lymph nodes which accompanied the application of transcutaneous administration devices or the delivery of antigens (vaccines and allergens) to the skin surface layer. This review presents our results from basic to clinical research on the development of transcutaneous formulations for vaccines and allergen-specific immunotherapy.

The route of administration dictates the immunogenicity of peptide-based cancer vaccines in mice.

Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Peptide vaccines to elicit CTLs in the clinic have routinely been administered in the same manner as vaccines designed to induce antibody responses: injected subcutaneously and in many instances using Freund's adjuvant. We report here that peptide vaccines and poly-ICLC adjuvant administered via the unconventional intravenous route of immunization generate substantially higher CTL responses as compared to conventional subcutaneous injections, resulting in more successful antitumor effects in mice. Furthermore, amphiphilic antigen constructs such as palmitoylated peptides were shown to be better immunogens than long peptide constructs, which now are in vogue in the clinic. The present findings if translated into the clinical setting could help dissipate the wide-spread skepticism of whether peptide vaccines will ever work to treat cancer.

PREVENTION OF ACUTE PANCREATITIS DURING ENDOSCOPIC TRANSPAPILLARY INTERVENTIONS

Aim. To identify the major risk factors of acute postoperative pancreatitis, to determine optimal volume of drug prevention, to study the possibility of intravenous administration of octreotide 600 mcg/ml in transpapillary endoscopic interventions. Material and Methods. In group I (72 patients) prevention of acute post-manipulation pancreatitis prior to endoscopic transpapillary interventions included intravenous administration of octreotide 600 mcg diluted in 60 ml 0.9% sodium chloride solution (NaCl). On the day of endoscopic intervention octreotide was administered fractionally 200 mcg 3 times per day. In group II (78 patients) acute pancreatitis was prevented by subcutaneous injection of octreotide 100 mcg before endoscopic intervention and subsequent 3-fold subcutaneous injection of 100 mcg on the day of surgery. Results. Risk factors of acute pancreatitis are young age, difficult cannulation of major duodenal papilla, atypical papillosphincterotomy, contrast injection into pancreatic duct. It is proved that intravenous administration of octreotide 600 mcg/ml reduces the risk of acute pancreatitis and transient hyperamylasemia from 16.7% and 19.2% to 11.1% and 16.7% respectively compared with conventional subcutaneous injection (100 mcg). Thus, it reduces the duration ( p < 0.016) and severity of hyperamylasemia (p < 0.005). Conclusion. Intravenous administration of octreotide 600 mcg/day is more effective and convenient compared with conventional scheme to prevent acute postmanipulation pancreatitis.

Cationic Niosomes for Enhanced Skin Immunization of Plasmid DNA-Encoding Ovalbumin via Hollow Microneedles.

The purpose of the present study was to evaluate the use of cationic niosomes composed of Span20:cholesterol:cationic lipid (N 1,N 1-dimyristeroyloxyethyl-spermine) at the molar ratio of 2.5:2.5:0.5mM combined with hollow microneedle (MN) devices for in vivo skin immunization of plasmid DNA-encoding ovalbumin (pOVA). The results revealed that using hollow MNs with cationic niosomes for pOVA penetration successfully induced both humoral and cell-mediated immune responses including immunoglobulin G (IgG) antibody responses, interleukin-4 (IL-4), and interferon gamma (IFN-γ) cytokine secretion. When using hollow MNs with cationic niosome/pOVA complexes, the immune response was superior to naked pOVA, which testifies the increased amount of IgG antibody responses and cytokine secretion. In comparison with conventional subcutaneous (SC) injections, using hollow MNs with cationic niosome/pOVA complexes induced a higher level of both IgG immune response and cytokine release. Moreover, a group of mice immunized with hollow MNs did not show infection or bleeding on the skin. Consequently, targeted delivery of pOVA using cationic niosomes combined with hollow MNs might prove a promising vaccination method for skin vaccination.

Implantable batteryless device for on-demand and pulsatile insulin administration

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin.

The aim of this study was to investigate the use of different types of microneedles (MNs) and nanocarriers for in vitro skin permeation and in vivo immunization of plasmid DNA encoding ovalbumin (pOVA). In vitro skin permeation studies indicated that hollow MNs had a superior enhancing effect on skin permeation compared with solid MN patches, electroporation (EP) patches, the combination of MN and EP patches, and untreated skin. Upon using hollow MNs combined with nanocarriers for pOVA delivery, the skin permeation was higher than for the delivery of naked pOVA, as evidenced by the increased amount of pOVA in Franz diffusion cells and immunoglobulin G (IgG) antibody responses. When the hollow MNs were used for the delivery of nanocarrier:pOVA complexes into the skin of mice, they induced a stronger IgG immune response than conventional subcutaneous (SC) injections. In addition, immunization of mice with the hollow MNs did not induce signs of skin infection or pinpoint bleeding. Accordingly, the hollow MNs combined with a nanocarrier delivery system is a promising approach for delivering pOVA complexes to the skin for promoting successful immunization.

Practical use of insulin in diabetes mellitus

Insulin therapy is the cornerstone of treatment in patients with type 1 diabetes mellitus (DM) and advanced type 2 DM. Over the years, insulin treatment has advanced from animal insulin to recombinant insulin with more efficiency and fewer side effects and from short-acting conventional insulin to ultrashort and long-acting insulin analogs to mimic various phases of physiological insulin secretion. Various insulin delivery systems from conventional subcutaneous insulin injection using insulin syringe to pen device, subcutaneous insulin infusion pumps, and inhaled insulin to artificial pancreas are now available. Proper insulin injecting techniques and patient education on self-monitoring of blood glucose and insulin dose titration are of utmost importance for effective insulin therapy.

Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities.

Diabetes mellitus is characterised by progressive β-cell destruction and loss of function, or loss of ability of tissues to respond to insulin. Daily subcutaneous insulin injection is standard management for people with diabetes, although patient compliance is hard to achieve due to the inconvenience of injections, so other forms of delivery are being tested, including oral administration. This review summarises the developments in oral insulin administration. The PubMed database was consulted to compile this review comparing conventional subcutaneous injection of insulin to the desired oral delivery. Oral administration of insulin has potential benefits in reducing pain and chances of skin infection, improving the portal levels of insulin and avoiding side effects such as hyperinsulinemia, weight gain and hypoglycaemia. Although oral delivery of insulin is an ideal administration route for patients with diabetes, several physiological barriers have to be overcome. An expected low oral bioavailability can be attributed to its high molecular weight, susceptibility to enzymatic proteolysis and low diffusion rate across the mucin barrier. Strategies for increasing the bioavailability of oral insulin include the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for endogenous receptor-mediated absorption. These may help significantly increase patient compliance and disease management.

Current opportunities and challenges in intradermal vaccination.

The skin is an attractive site for immunization in humans and animals, owing to its resident population of dendritic cells and macrophages along with extensive vascularization by lymphatic vessels and blood capillaries. In addition to these physiological attributes, the intradermal route for vaccine delivery also presents a less-invasive alternative to conventional subcutaneous or intramuscular injections. This may offer compliance and convenience advantages for a wide range of stakeholders including patients, healthcare providers, veterinarians, animal owners and animal producers. This review discusses the current developments in intradermal vaccination for human and veterinary applications, with particular focus on the skin immunology, vaccine antigens and adjuvants and delivery systems.

Application of recombinant human growth hormone in improving difficult weaning

Objective To observe the applicated value of recombinant human growth hormone （ r-hGH） ther-apy in improving difficult weaning .Methods 40 patients with difficult weaning were randomly divided into the treat-ment group （20 cases） and control group （20 cases）.The control group received routine ICU treatment .The treat-ment group was given the conventional treatment and subcutaneous injection of r -hGH 8IU,1 time a day,a total of 14 days.The serum total protein,albumin,oxygenation index,peak of blood glucose,independent tidal volume changes were observed before and after treatment , the success rate and mortality rate were compared .Results After treat-ment,the total protein,albumin,tidal volume of the treatment group were （68.1 ±13.4） g/L,（40.8 ±6.0） g/L, （432 ±57）mL,which were significantly higher than those before treatment [（52.3 ±12.5）g/L,（28.4 ±4.5）g/L, （278 ±54）mL]（t=3.856,7.394,8.771,all P〈0.05）.While after treatment,the total protein,albumin,tidal vol-ume in the control group were （58.4 ±14.2）g/L,（31.0 ±5.8）g/L,（398 ±48）mL,compared with before treatment （53.2 ±13.3）g/L,（28.1 ±4.2）g/L,（271 ±49）mL,the differences were not statistically significant （all P〉0.05）.The success rate was 85% in the treatment group,which was higher than 50% in the control group（χ2 =4.103,P〈0.05）.In the treatment group,3 cases died,in the control group 9 cases died,there was statistically signif-icant difference between the two groups （χ2 =4.286,P〈0.05）.Conclusion r-hGH can improve the nutritional sta-tus of critically ill patients ,increase the strength of the respiratory muscles ,improve lung function ,help to improve the weaning rate . Key words: Human growth hormone; Ventilators, mechanical