CN103417978A

CN103417978A - Hypromellose enteric empty capsule gelated by gellan gum and potassium citrate

Info

Publication number: CN103417978A
Application number: CN2013103462224A
Authority: CN
Inventors: 陈光伦; 张强
Original assignee: CHONGQING HENGSHENG CAPSULES FOR MEDICINES Co Ltd
Current assignee: SICHUAN TIANSHENG PHARMACEUTICAL CO., LTD.
Priority date: 2013-08-11
Filing date: 2013-08-11
Publication date: 2013-12-04
Anticipated expiration: 2033-08-11
Also published as: CN103417978B

Abstract

A hypromellose enteric empty capsule gelated by gellan gum and potassium citrate belongs to technical field of empty capsule production, is characterized in that hypromellose is used as a main raw material and mixed with the gellan gum and potassium citrate to prepare the empty capsule, and has the benefits that the disintegration is timely, moisture content is low, the empty capsule is suitable for medicines which have strong hygroscopicity and are sensitive to water, the influence of dissolved mediums on a capsule shell is small, the medication compliance is high, the storage period is long, the empty capsule can not go bad within 3-4 years, requirements on storage and transportation conditions are low, the empty capsule is less susceptible to fragmentation at a low-moisture environment, is insusceptible to deformation at a high-temperature environment, and has low probabilities of rottenness and deterioration; the empty capsule is made from pure vegetable fibers, and can meet requirements of all cultural backgrounds and religious groups; the manufacturing process is almost free from pollution, tailings can be again dissolved for reuse; frequently-used surface-active agents and plasticizers are eliminated, the gelating speed is accelerated only by using the potassium citrate to help the gellan gum to condense so as to reduce the gelating temperature, accordingly, the additives are reduced, and the production cost is reduced; the empty capsule is suitable for mass promotion.

Description

Hypromellose enteric hollow capsule by gellan gum and potassium citrate gel

Technical field

The invention belongs to the Capsules production technical field, particularly a kind ofly take the vegetalitas enteric hollow capsule by gellan gum and potassium citrate gel prepared as raw material by hypromellose.

Background technology

Capsules is comprised of the refining cap formed of medicinal materials, body two joint capsule shells, for the splendid attire solid drugs; As make powder, health product, medicament etc. by oneself, for the user has solved difficult entrance, the poor problem of mouthfeel, really realized that good medicine is no longer bitter to the taste; Because Capsules is easy to swallow, that can very effectively cover content makes us uncomfortable taste and abnormal smells from the patient, welcome by the patient.

[0003] current Capsules mainly contains gelatine capsule and the various vegetalitas capsule of animality, in China, the gelatin Capsules accounts for the overwhelming majority, at present, the gelatin Capsules has been widely used in food, health food and medicine field, in recent years, along with the development of China's modernization of Chinese medicine, capsule accounts for the ratio of whole pharmaceutical preparation total amounts also in constantly rising.

[0004] but obviously there is the slow defect of disintegration rate in gelatine capsule, simultaneously huge gelatin Capsules market and industrial chain thereof also brought many quality problems and security risk.After " chromium exceed standard capsule event ", the safety problem that capsule produces has received more concern; Simultaneously, along with the generation of Animal diseases as " bovine spongiform encephalopathy " " foot and mouth disease ", people have produced very large uneasiness to utilizing animal's leather, bone to produce the gelatin raw material, and there is great potential safety hazard in the Capsules that the animal gelatin of take is main production.

In view of this, scientific research institution has strengthened the research to the vegetalitas capsule both at home and abroad, successively developed up to now multiple non-gelatin Capsules, as the patent No. 200810138256.3 has been announced " a kind of cellulose and plant polyoses capsule ", this patent is passed through the pulullan polysaccharide of 68%-88%, the hypromellose of 10%-30%, the gel of 1%-3%, the flocculation aid of 0.1%-0.5%, the surfactant of 0.1%-0.5% and the pigment of 0.1%-0.3% are prepared into glue and dip in glue and form, this patent has solved the gelatine capsule disintegration rate slowly and the problem of potential safety hazard, but obviously inadequate aspect the film property of capsule body and storage-stable, with some drugs in capsule is existed to harmful effect, surfactant has wherein been prohibited use.

Summary of the invention

Technical problem to be solved by this invention is: for the deficiencies in the prior art, provide a kind of and take hypromellose as the main raw material(s) preparation, carry out gel by gellan gum and potassium citrate, there is no potential safety hazard, can Long-term Storage, disintegrate fast, the minimum enteric hollow capsule to drug influence in capsule, with the raising safety of taking medicine, improve medical effect.

For solving the problems of the technologies described above, the technical solution adopted in the present invention is a kind of hypromellose enteric hollow capsule by gellan gum and potassium citrate gel, it is characterized in that preparation method is as follows.

(1) get hypromellose 50kg, in the purified water that to put into the 165-175L temperature be 80-100 ℃, by the mixing speed of 1550-1650rpm, constantly stir and naturally cool to 22-28 ℃, then be incubated standing 60-90min, again solution is heated to 40-45 ℃, obtains hypromellose solution.

(2) getting gellan gum 300-350g is dissolved in the purified water that the 15-20L temperature is 40-45 ℃, stir 3-5min by the speed of 2550-2650rpm, join until completely dissolved in hypromellose solution, continue to stir 2-3min, mix homogeneously by the speed of 1550-1650rpm.

(3) getting potassium citrate 280-300g joins in hypromellose solution, continue to stir and naturally cool to 22-28 ℃ by the speed of 1550-1650rpm, again solution is heated to 40-45 ℃ after standing 2-3min, then be incubated standing 60-120min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 30-35 ℃ of room temperature.

(4) the capsule rod is immersed in hypromellose phthalic acid fat organic solution, then take out dry.

(5) finally by the demoulding, cut, fit, make the hypromellose enteric hollow capsule.

Its preferred preparation method is as follows.

(1) get hypromellose 50kg, in the purified water that to put into the 170L temperature be 90 ℃, by the mixing speed of 1600rpm, constantly stir and naturally cool to 25 ℃, then be incubated standing 75min, then solution is heated to 42.5 ℃, obtain hypromellose solution.

(2) get gellan gum 325g and be dissolved in the purified water that the 17.5L temperature is 42.5 ℃, by the speed of 2600rpm, stir 4min, join until completely dissolved in hypromellose solution, continue to stir 2.5min, mix homogeneously by the speed of 1600rpm.

(3) getting potassium citrate 290g joins in hypromellose solution, continue to stir and naturally cool to 25 ℃ by the speed of 1600rpm, solution is heated to 42.5 ℃ again after standing 2.5min, then be incubated standing 90min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 32.5 ℃ of room temperatures.

In the present invention, the inventor is through long-term experiment many times, all need to add activating agent and plasticizer just can obtain good colloidal solution, the effect that hypromellose is added to the water from low temperature to the high-temperature digestion is undesirable, also undesirable from high temperature to the dissolution in low temperature conversely, the constant temperature effect is more undesirable, carry out gel after heating up conversely again after afterwards once because of carelessness unintentionally from high temperature to the dissolution in low temperature, activity and the plasticity of finding hypromellose solution improve greatly, film property is better, again by experiment repeatedly, find that the inventive method no longer needs to add surfactant and plasticizer, can complete and dip in glue equally, solved in this area and wished to reduce the difficult problem of additive always, greatly reduce on the impact of medicine with to patient's side effect.

The invention has the beneficial effects as follows and take hypromellose as the enteric hollow capsule material, the multiple advantage that has of hypromellose that made Capsules possess, it is mainly manifested in stable chemical nature, without cross-linking reaction, and softgel shell disintegrate simultaneously, so disintegrate is very timely; Water content is low, can be controlled in 8% left and right, reduces medicine hygroscopicity risk, is suitable for strong for hygroscopicity and to medicine, particularly health product and the cosmetics of minute water sensitive; Dissolution medium is little on the softgel shell impact, and little to the adhesion strength of esophagus, the medication compliance is high; Easily store, effect duration is long, 3-4 never degenerates, low to the conditional request stored and transport, and under low wet environment, is difficult for friability, friability under the 35%RH environment≤20%, not yielding under hot environment, utricule distortion≤1% under 80 ℃ of environment, do not contain protein in raw material, make existence and the breeding of antibacterial lose necessary condition, be difficult for rotting; Pure plant fiber, raw material sources are relatively simple, meet all culture backgrounds and religions belief crowd's requirement; Safe, without the zoonosis risk, without hormone residual in animal body, medicine and other harmful substances; Almost pollution-free in production process, but tailing secondary back dissolving is utilized; Save surfactant commonly used and plasticizer, only by potassium citrate, helped the cold glue that condenses to reduce gelling temp and accelerate gelation rate, reduced additive, reduced production cost, be applicable to large-scale popularization.

The specific embodiment

Below in conjunction with embodiment, the invention will be further described, and following examples are intended to illustrate the present invention rather than limitation of the invention further, should not limit the scope of the invention with this.

Embodiment 1.

Get hypromellose 10kg, in the purified water that to put into the 33L temperature be 80 ℃, by the mixing speed of 1550rpm, constantly stir and naturally cool to 22 ℃, then be incubated standing 60min, then solution is heated to 40 ℃, obtain hypromellose solution; Then get gellan gum 60g and be dissolved in the purified water that the 3L temperature is 40 ℃, by the speed of 2550rpm, stir 5min, join until completely dissolved in hypromellose solution, continue to stir 3min, mix homogeneously by the speed of 1550rpm; Then getting potassium citrate 56g joins in hypromellose solution, continue to stir and naturally cool to 22 ℃ by the speed of 1550rpm, solution is heated to 40 ℃ again after standing 2min, then be incubated standing 60min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 30 ℃ of room temperatures; Again the capsule rod is immersed in hypromellose phthalic acid fat organic solution, then take out dry; Finally, by the demoulding, cut, fit, make the hypromellose enteric hollow capsule.

Embodiment 2.

Get hypromellose 50kg, in the purified water that to put into the 170L temperature be 90 ℃, by the mixing speed of 1600rpm, constantly stir and naturally cool to 25 ℃, then be incubated standing 75min, then solution is heated to 42.5 ℃, obtain hypromellose solution; Then get gellan gum 325g and be dissolved in the purified water that the 17.5L temperature is 42.5 ℃, by the speed of 2600rpm, stir 4min, join until completely dissolved in hypromellose solution, continue to stir 2.5min, mix homogeneously by the speed of 1600rpm; Then getting potassium citrate 290g joins in hypromellose solution, continue to stir and naturally cool to 25 ℃ by the speed of 1600rpm, solution is heated to 42.5 ℃ again after standing 2.5min, then be incubated standing 90min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 32.5 ℃ of room temperatures; Then the capsule rod is immersed in hypromellose phthalic acid fat organic solution again, then take out again dry; Finally, by the demoulding, cut, fit, make the hypromellose enteric hollow capsule.

Embodiment 3.

Get hypromellose 100kg, in the purified water that to put into the 350L temperature be 100 ℃, by the mixing speed of 1650rpm, constantly stir and naturally cool to 28 ℃, then be incubated standing 90min, then solution is heated to 45 ℃, obtain hypromellose solution; Then get gellan gum 700g and be dissolved in the purified water that the 40L temperature is 45 ℃, by the speed of 2650rpm, stir 3min, join until completely dissolved in hypromellose solution, continue to stir 2min, mix homogeneously by the speed of 1650rpm; Then getting potassium citrate 600g joins in hypromellose solution, continue to stir and naturally cool to 28 ℃ by the speed of 1650rpm, solution is heated to 45 ℃ again after standing 3min, then be incubated standing 120min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 35 ℃ of room temperatures; Then the capsule rod is immersed in hypromellose phthalic acid fat organic solution again, then take out again dry; Finally, by the demoulding, cut, fit, make the hypromellose enteric hollow capsule.

Claims

1. by the hypromellose enteric hollow capsule of gellan gum and potassium citrate gel, it is characterized in that preparation method is as follows:

(1) get hypromellose 50kg, in the purified water that to put into the 165-175L temperature be 80-100 ℃, by the mixing speed of 1550-1650rpm, constantly stir and naturally cool to 22-28 ℃, then be incubated standing 60-90min, again solution is heated to 40-45 ℃, obtains hypromellose solution;

(2) getting gellan gum 300-350g is dissolved in the purified water that the 15-20L temperature is 40-45 ℃, stir 3-5min by the speed of 2550-2650rpm, join until completely dissolved in hypromellose solution, continue to stir 2-3min, mix homogeneously by the speed of 1550-1650rpm;

(3) getting potassium citrate 280-300g joins in hypromellose solution, continue to stir and naturally cool to 22-28 ℃ by the speed of 1550-1650rpm, again solution is heated to 40-45 ℃ after standing 2-3min, then be incubated standing 60-120min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 30-35 ℃ of room temperature;

(4) the capsule rod is immersed in hypromellose phthalic acid fat organic solution, then take out dry;

2. the hypromellose enteric hollow capsule by gellan gum and potassium citrate gel according to claim 1 is characterized in that preparation method is as follows:

(1) get hypromellose 50kg, in the purified water that to put into the 170L temperature be 90 ℃, by the mixing speed of 1600rpm, constantly stir and naturally cool to 25 ℃, then be incubated standing 75min, then solution is heated to 42.5 ℃, obtain hypromellose solution;

(2) get gellan gum 325g and be dissolved in the purified water that the 17.5L temperature is 42.5 ℃, by the speed of 2600rpm, stir 4min, join until completely dissolved in hypromellose solution, continue to stir 2.5min, mix homogeneously by the speed of 1600rpm;

(3) getting potassium citrate 290g joins in hypromellose solution, continue to stir and naturally cool to 25 ℃ by the speed of 1600rpm, solution is heated to 42.5 ℃ again after standing 2.5min, then be incubated standing 90min, obtain flooding stable colloidal solution, then dip in glue Cheng Mo, then drying obtains dry capsule rod under 32.5 ℃ of room temperatures;