Relationship between dipalmitoyl lecithin and respiratory distress syndrome

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relationship between dipalmitoyl lecithin and respiratory distress syndrome

Relationships among human amniotic fluid dipalmitoyl lecithin, postpartum respiratory compliance, and neonatal respiratory distress syndrome. Article in Clinical. C The lecithin/sphingomyelin ratio in the amniotic fluid is likely to be greater than two.D The concentration of dipalmitoyl phosphatidylcholine in the amniotic fluid Which of the following statements about respiratory distress syndrome RDS is. , The ultrastructure of the lungs of lambs: The relation of osmiophilic inclusions layer to fetal maturation and experimentally produced respiratory distress, Amer. M., , Synthesis of dipalmitoyl lecithin by alveolar macrophages, J. Clin. findings as related to the respiratory distress syndrome, Pediatrics

When you were a young child, one of your parents probably showed you how a sewing needle could be placed very carefully on top of a dish of water, and the needle would float.

This was because molecules of water are attracted to one another; the water molecules holding on to one another under the pin hold the pin afloat!

Respiratory distress syndrome.

We known that a drop of water on a table top will not spread out into a layer which is one molecule thin; again, water molecules are attracted to one another, and they pile up surface tension rather than spreading out into such a thin layer!

Above is a very clever photograph of a soap bubble the media is, of course, water by Walter Wick, whose book "A Drop of Water" is a must read if you have little children interested in science and water! Detergents reduce surface tension in fluids In a bubble, surface tension, or the attraction between water molecules, is trying to collapse the bubble. The inward force in a small bubble is greater than the inward force in a larger bubble containing the same amount of water.

That means that the inward force in a small bubble is sufficient to make a larger bubble expand and burst! This strange sounding relationship means that there is more "collapsing force" exerted within a small bubble than in a larger bubble containing the same amount of water.

Perhaps an even simpler way to understand this mathematical concept is to examine LaPlace's Law.

Respiratory Distress syndrome- Case discussion

Direction of Forces Trying to Collapse a Bubble All of the water molecules in the walls of the bubble are trying to move closer to one another.

The net effect is to reduce the surface area of the bubble, at the same time reducing the diameter of the bubble and collapsing the overall size of the bubble! Now, think of the alveoli in the lung as bubbles. Alveoli are spherical, like bubbles, and the alveoli are lined with fluid.

Constant fluid secretion keeps the alveolar lining moist!

relationship between dipalmitoyl lecithin and respiratory distress syndrome

Remember, the alveolar tissue is living tissue and if it is not bathed in fluid it will die. The skin cells covering our body are not bathed in fluid, but that is because our outermost epidermal layers are not living tissue! As we inhale, our lungs expand and the surface area of the "bubbles" alveoli increase.

This means that, as we inhale, there is a decrease in the inward pressure associated with surface tension trying to collapse our lungs. Note however, that as we inflate our lungs, we stretch elastic tissues within our lungs and chest wall that will make our lungs collapse back down as we exhale!

As we exhale, our lungs are reduced in size and the surface area of the bubbles alveoli decrease. This means that, as we exhale, there is an increase in the inward pressure associated with surface tension trying to collapse our lungs. Note however, that as we deflate our lungs, the elastic tissues are brought closer to resting position, and so the elastic tissues do not work as hard to collapse our lungs!

The lung has a special way to decrease surface tension in the alveolar walls. In the alveolar walls are "surfactant cells" type II pneumocytes. Surfactant cells are large cells with big, plump nuclei that easily differentiate them from alveolar and capillary endothelial cells.

Surfactant cells secrete surfactant, a mixture of protein-phospholipid complexes which acts like a strong detergent Surfactant Protein B and C: Recall that detergents reduce surface tension, reducing the pressure trying to collapse bubbles! The primary constituent of surfactant is a phospholipid called dipalmitoyl lecithin or dipalmitoyl phosphatidyl choline ie. Evidence of the presence of surfactant can be seen in fluid collected from the airways of victims of pulmonary edema; this fluid contains bubbles which are very stable and remain for hours after the time of death.

Oh, by the way, good sources of lecithin are soybean, corn and egg yolks! The surface tension of water is high and constant, regardless of surface area. As examples of unsaturated fatty acids from which the radicals can be derived oleic acid and linoleic acid may be mentioned. As neutral lipids used in the present invention, there are triglycerides, diglycerides and monoglycerides of which triglycerides or diglycerides whose main ingredients are saturated straight chain fatty acid acyloxy radicals having 14 to 25 carbon atoms are desirable.

As examples of neutral lipids, there are trimyristin, tripalmitin, tristearin, triarachidin, dimyristin, dipalmitin, distearin, diarachidin, trilinolein, triolein, dilinolein, and diolein.

Fatty acids used in this invention are preferably those straight chain fatty acids such as myristic acid, palmitic acid, stearic acid, and arachidic acid, as saturated fatty acids, and oleic acid, elaidic acid, linoleic acid and linolenic acid, as unsaturated fatty acids. The phospholipids to be contained in the artificial lung surfactant of the present invention, may comprise a combination of phosphatidyl choline and cardiolipin, a combination of phosphatidyl choline and phosphatidyl glycerol, or a combination of phosphatidyl choline, cardiolipin, and phosphatidyl glycerol.

If the above-mentioned instructions as to the content of main ingredients are not observed, the object of the present invention can not be achieved.

In the present invention, other phospholipids, carbohydrates, etc. No limit is set to the method and means of mixing; however, to cite one example, a homogeneous mixture can be prepared easily by dissolving the ingredients in a common solvent such as chloroform, and then removing the solvent from the solution. Its stability index is 1. These values generate a specific hysteresis loop as shown in Figure 1 similar to that of natural lung surfactant to indicate that the obtained artificial lung surfactant has a high surface activity.

Since the artificial lung surfactant of this invention is usually obtained as a wax, it is advisable to administer it by dispersing it in water or an electrolytic solution such as saline solution or by forming it into a powder by use of other medically permissible powders as excipients. The preparation of a dispersion can be achieved by dispersing the waxy surfactant directly in a liquid; however, for reasons of sanitation and preparing procedure, a powder may be prepared beforehand by lyophilizing a dispersion of said waxy surfactant in a solution containing an excipient, as case may require.

The thus formed powder is then dispersed in water at the time of its administration. As medically permissible powders, those powders which are water-soluble and innocuous are desirable and it is proper to use it at a ratio of 2 to 50 parts by weight against 1 part by weight of the artificial lung surfactant, especially 5 to 20 parts by weight is recommendable.

As desirable powders, amino acids and saccharides may be mentioned because they do not degrade the surface activity. As the amino acids, there are essential amino acids such as glycine, alanine, tryptophane and cystine, and as the saccharides, there are glucose, mannitol and sorbitol.

As the methods of preparing a powder, it can be prepared simply by thoroughly mixing the artificial lung surfactant with medically permissible powders.

Respiratory Distress Syndrome

However, it is preferable to prepare a powder by dissolving the surfactant in an organic solvent, to which a proper quantity of fine powder of amino acid was added to obtain a homogeneous dispersion. The obtained dispersion is put into for instance a rotary evaporator and evaporated to dryness under reduced pressure with rotation and stirring. The obtained powder is further pulverized into fine powder of uniform particle size to give a desired powder.

In another method of preparing a powder, the surfactant is uniformly dispersed in water or an aqueous solution of salt.

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A prescribed amount of said saccharide or amino acid is dissolved in the obtained dispersion to prepare a homogeneous dispersion. The dispersion is then lyophilized and the obtained powder is further pulverized into fine powder having a uniform particle size to give the desired powder. The artificial lung surfactant attaches to the surfaces of the powdery substance uniformly and can be used as a preparation having the form of powder. Since the artificial lung surfactant thus prepared in the form of powder makes no change in its surface activity and has the same degree of surface activity as the natural lung surfactant as mentioned herein before, the powder of the artificial lung surfactant of this invention can reasonably be expected to have enough efficacy as a remedy for respiratory distress syndrome such as IRDS, etc when administered by inhalation or nebulization.

In the present invention, the measurement of surface tension and the calculation of stability index of the artifical lung surfactant were conducted according to the following procedures.

In measuring the surface tension, an improved type of Wilhelmy balance of Acoma make was used. In the case where the specimen was a dispersion, the measurement was made after 50 ml of saline solution used in the adjustment was replaced with 50 ml of specimen dispersion.

In the case where the specimen was a dry substance or powder, a very small amount of the specimen powder was placed gently on 50 ml of saline solution. The surface film area was compressed cyclically in the range of a maximum of 40 CM 2 to a minimum of 13 CM 2 at the rate of 0. The minimum surface tension y min value, maximum surface tension y maxand area surrounded by the hysteresis loop were obtained from the hysteresis loop converged invariantly at the 5th or 6th cycling from the start.

The stability index S. The measurement of surface activity in vivo was made according to the method proposed by Kataoka et al. Journal of Japanese Medical Society for Biological Interface 13 2 61 by means lung-lavage as follows.

relationship between dipalmitoyl lecithin and respiratory distress syndrome

An adult rabbit had its trachea cut open under an anesthetic and was given lung lavage five times at intervals of 10 minutes with 75 ml of saline solution through a tube inserted from the cut opening into the trachea. The lung lavages were conducted by slowly injecting a saline solution and then sucking up to remove it.

The treated rabbit was kept under respiratory control by use of a respiratory based on inspiratory intratracheal pressure of 20 cm of mercury and PEEP positive end expiratory pressure of 40 mbar 3 cm of mercury under pure oxygen.

For comparison's sake, the same amount of saline solution was administered according to the same method. The following Comparison and Examples, in which percents are by weight, illustrate the invention in detail. Reference 1 Preparation of natural lung surfactant A lung surfactant was separated following the procedure mentioned below which was based on the method proposed by M. The extract was subjected to low speed centrifugation at a rate of 1, rpm for 30 minutes to obtain a supernatant.

The obtained supernatant was centrifuged at a high rate of 7, rpm for 60 minutes to give a centrifugate. The centrifugate was dispersed in a saturated saline solution specific gravity 1.

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The dispersion was centrifuged at a rate of 7, rpm for 30 minutes and the upper white layer was collected, which was then dialyzed against cooled distilled water and lyophilized to obtain a natural lung surfactant. In accordance with the procedure proposed by Folch, the obtained natural lung surfactant was dissolved in a mixed solvent of chloroform and methanol volume ratio 2: Its surface activity is shown in Table 1.

The lipids were solubilized with SDS and subjected to electrophoresis analysis of polyacrylamide gel disk type according to the ordinary method.

relationship between dipalmitoyl lecithin and respiratory distress syndrome

A single band was observed at a mobility of 0. Example 1 mg of L-a-dipalmitoyl phosphatidyl choline DPPCmg of L-a-dipalmitoyl phosphatidyl glycerol DPPGand mg of tripalmitin were mixed and dissolved in 50 ml of chloroform to obtain a homogeneous solution.

The solution was placed in a rotary evaporator and evaporated at room temperature under reduced pressure to dryness and dried further at a high degree of vacuum to obtain a white waxy solid substance. The result is shown in Table 1. The hysteresis loop was large i.

As seen from Figure 2, the partial pressure of oxygen Pa02 in the blood of the rabbits subjected to lung lavage presented the same rise as the natural lung surfactant to show the recovery of respiratory function. The solution was evaporated to dryness according to Example 1 to obtain a white waxy solid substance. Its surface activity was determined according to Example 1 and the obtained result is shown in Table 1.

As shown in Figure 2, the partial pressure of oxygen Pa02 in the blood presented the same rise as the natural lung surfactant as in Example 1 to show the recovery of respiratory function.

A white solid substance was obtained from the solution according to the same procedure as Example 1. Then mg of this substance was dispersed homogeneously in 50 ml of saline solution and the surface activity was measured with the use of a Wilhelmy balance. The result showed that it had an excellent surface activity as shown in Table 1. Example 4 mg of L-a-DPPC, mg of L-a-DPPG, and mg of tristearin were weighed respectively, dissolved in 50 ml of chloroform, and evaporated to dryness to obtain a white waxy substance.

This dispersion was then lyophilized to obtain a white dry substance.