阅读说明：本技术 链式药物结构及其制备装置和储存装置 (Chain medicine structure and preparation facilities and storage device thereof ) 是由 董永华 董睿 于 2018-03-26 设计创作，主要内容包括：本发明提供了链式药物组合物(结构或剂型),包括像火车车厢一样线性串联的分段。当药物组合物被施加于患者身体,部分分段可以借助仪器“可见”,但是另外一部分却不可见。然而,这些“不可见”分段可以从“可见”的分段来估计,推断,计算或推测。这些“不可见”分段可以用于结合糖缺乏对瘤内乳酸酸中毒进行中和以控制肿瘤,以及其他应用。(The present invention provides chained pharmaceutical compositions (structures or dosage forms) comprising segments linearly connected in series like a railway car. When the pharmaceutical composition is applied to the patient's body, part of the segments may be "visible" by the instrument, but another part may not be visible. However, these "invisible" segments can be estimated, inferred, calculated, or inferred from "visible" segments. These "invisible" segments can be used to neutralize intratumoral lactic acidosis in conjunction with sugar deficiency to control tumors, among other applications.)

1. A chained pharmaceutical composition (structure or dosage form) comprising a head portion segment and a body portion segment, both linearly arranged in series like two adjacent cars of a train,

wherein the position of the head segment is observable by the person with the aid of the apparatus when the pharmaceutical composition is administered into the patient; with the aid of the instrument, the position of the body segment cannot be observed by a person, but can be inferred from the observed position of the head segment.

2. The chained pharmaceutical composition of claim 1, further comprising a tail segment that can be observed by a human with the aid of the device,

wherein the body section is sandwiched between the head section and the tail section,

wherein the head section, the body section and the tail section are linearly connected in series like three consecutive cars of a train, an

Wherein the position of the body segment can be inferred from the observed position of the head segment and the position of the tail segment.

3. The chained pharmaceutical composition of claim 1, wherein the arrangement of the head and body segments is repeated one or more times to form a (body-head) n structure, wherein n is an integer and n ≧ 2, and 2n head/body segments are arranged in series like 2n consecutive cars of a train.

4. The chained pharmaceutical composition of claim 3, further comprising a tail segment that can be observed by a human with the aid of the device to form a tail- (body-head) n structure, where n is an integer and n ≧ 2, and 2n +1 head segments/body segments/tail segments are arranged in series like 2n +1 consecutive cars of a train.

5. The chain pharmaceutical composition of claim 1, which is confined in a lumen having a lengthwise tubular structure (like a train confined in a tunnel).

6. The chained pharmaceutical composition of claim 5, wherein the lumen has an inner diameter at a location of the lumen, and any segment (head segment, body segment, or optional tail segment) is constrained to have the same diameter at the location as the inner diameter.

7. The chain pharmaceutical composition of claim 5, wherein the tubular structure is a human or animal blood vessel, a catheter or a combination thereof, wherein the combination is defined as the catheter is inserted into the blood vessel and the two are connected, communicating or joined intraluminally.

8. The chained pharmaceutical composition of claim 1, wherein the device is an X-ray based imaging device, an ultrasound device, a Magnetic Resonance Imaging (MRI) device, or a combination thereof.

9. The chained pharmaceutical composition of claim 8, wherein the X-ray based imaging device is used for Computed Tomography (CT), radiography, fluoroscopy, or a combination thereof; and the blood vessel is referred to as an arteriole, or the blood vessel is located between an arteriole and a capillary downstream of the arteriole, the arteriole supplying blood to target cells such as tumor cells.

10. The chained pharmaceutical composition of claim 1, wherein the body segment is a liquid; the head part section is gas such as carbon dioxide; and the optional tail section is a gas such as carbon dioxide.

11. The chain pharmaceutical composition of claim 10, wherein the liquid is ethanol such as vinyl alcohol (ethanol).

12. The chained pharmaceutical composition of claim 11, wherein the therapeutic agent is dissolved, suspended or dispersed in ethanol, such as vinyl alcohol.

13. The chain pharmaceutical composition of claim 12, wherein the therapeutic agent comprises a basic substance.

14. The chained pharmaceutical composition of claim 13, wherein the basic substance comprises sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium ethoxide, potassium carbonate, potassium bicarbonate, potassium hydroxide, a primary amine, a secondary amine, a tertiary amine, an aliphatic amine, an aromatic amine, or any mixture thereof.

15. The chain type pharmaceutical composition according to claim 11, wherein the ethanol such as vinyl alcohol contains less than 0.1% by weight of water and has a volume of 0.0001-1 ml.

16. A medical device for combining and delivering the chained pharmaceutical composition of claim 1 into a lumen of a blood vessel, comprising:

a source of a head-segment material,

a tube of head section material (e.g., a channel within a catheter) for delivering head section material from the source of head section material directly into a vessel lumen,

a body segment material source, and

a body section material tube (e.g., a channel within a catheter) for delivering body section material directly from the source of body section material into the vessel lumen.

17. The medical device of claim 16, further comprising a main catheter insertable into the vessel lumen, wherein the head section material tube is connected to the main catheter such that the head section material from the head section material source is delivered into the vessel lumen through the main catheter; and, the body section material tube is connected to the main conduit such that body section material from the body section material source is delivered into the vessel lumen through the main conduit.

18. The medical device of claim 16, further comprising a controller that controls the time and amount that the head segment material and the body segment material are delivered into the vessel lumen such that the head segment and the body segment linearly serially resemble two adjacent cars of a train in the vessel lumen.

19. A medical storage device comprising a catheter for storing the chained pharmaceutical composition of claim 1.

20. The medical storage device of claim 19, further comprising a valve located between the head section and the body section, and separating the head section and the body section from each other.

Technical Field

The present invention relates to chained pharmaceutical compositions (structures or dosage forms), medical devices for preparing pharmaceutical compositions, and medical storage devices for sealing and storing pharmaceutical compositions. Although the present invention is exemplified by the release of a chain pharmaceutical composition into the lumen of a blood vessel, for example for the purpose of diagnosis and treatment such as embolism and cancer, and further for example for the purpose of controlling a tumor to neutralize intratumoral lactic acidosis by binding to the sugar deficiency of the tumor (neutral intracellular lactic acidosis combined with glucose depletion); it should be understood that the present invention may be applied to other technical fields.

Background

Sclerotherapy is a method for treating vascular or vascular malformations (vascular malformations) and the lymphatic system. Sclerosis is the thickening of the vessel wall and the interruption of blood flow. In foam sclerotherapy, a "foam sclerosant" is injected into a blood vessel using a pair of syringes, one containing the sclerosant and the other containing a gas, such as air. The sclerosant, such as sodium tetradecyl sulfate or polidocanol, is mixed with air or a physiological gas (e.g. carbon dioxide) in a syringe or by a mechanical pump.

For example, arteriovenous malformations (AVMs) are abnormal connections between arteries and veins that bypass the capillary system. Ethanol is a hardening agent well suited for the treatment of AVM. Ethanol hardens vascular endothelial cells (endothelialization), denatures endothelial proteins, and activates the coagulation system to cause blood clotting. However, in X-ray contrast-guided sclerotherapy, ethanol administration is not easily monitored and controlled. Thus, ethanol injected into a patient may run away and flow to some areas, causing tissue damage in that area.

Therefore, there is a need to overcome the above problems and also to conveniently and accurately deliver alkaline chemicals to tumors to bind the sugar deficiency of the tumor to neutralize intratumoral lactic acidosis. Advantageously, the present invention provides chained pharmaceutical compositions (structures or dosage forms) that exhibit a number of technical advantages, such as precise control of "stealth" chemicals in a patient, maximized and safe tumor control and sclerosing effects, and the like.

Disclosure of Invention

One aspect of the present invention provides a chained pharmaceutical composition (structure or dosage form) comprising a head segment and a body segment. The head section and body section are linearly arranged in series like two adjacent cars of a train. When administering the pharmaceutical composition into the patient, the person can observe the position of the head segment with the aid of the instrument. However, with the aid of the same instrument, the position of the body segment cannot be observed by a person. With the present invention, the location of a body segment can be estimated, inferred, calculated or inferred based on the observed head segment location.

Another aspect of the present invention provides a medical device for assembling and delivering the above-described chained pharmaceutical compositions into a lumen of a blood vessel. The device includes at least (1) a source of head-segment material, (2) a tube of head-segment material (e.g., a channel within a catheter) for delivering head-segment material directly from the source of head-segment material into a vessel lumen, (3) a source of body-segment material, and (4) a tube of body-segment material (e.g., a channel within a catheter) for delivering body-segment material directly from the source of body-segment material into a vessel lumen.

In a further aspect of the present invention, there is provided a drug storage device comprising a tube for storing the above-mentioned chained drug composition.

Another aspect of the invention provides methods of treating blood vessels and perivascular cells. The method comprises (i) providing a chain pharmaceutical composition as described above; (ii) administering the pharmaceutical composition into a patient; (iii) observing the position of the head segment with the aid of an instrument; (iv) from the observed head segment position estimate, the position of the body segment is inferred, calculated or inferred, wherein the position of the body segment cannot be directly observed by a person with the aid of the same instrument.

The above features and advantages and other features and advantages of the present invention are readily apparent from the following detailed description of the best modes for carrying out the invention when taken in connection with the accompanying drawings.

Drawings

The present invention is illustrated by way of example in the accompanying drawings, which are not to be construed as limiting the invention, and in which like references indicate similar elements. All the figures are only schematic and conventionally show parts which are necessary for elucidating the invention. For simplicity and clarity of illustration, elements illustrated in the figures and discussed below are not necessarily drawn to scale. Well-known structures and devices are shown in simplified, omitted, or merely suggested form in order to avoid unnecessarily obscuring the present invention.

Fig. 1 schematically shows a chain type pharmaceutical composition administered to a patient according to an embodiment of the present invention.

Fig. 2 schematically shows a medical device according to a first embodiment of the invention for assembling and delivering a chain-type pharmaceutical composition to a vessel lumen.

Fig. 3 schematically shows a medical device according to a second embodiment of the invention for assembling and delivering a chain-type pharmaceutical composition to a lumen of a blood vessel.

Fig. 4 schematically shows a medical device according to a third embodiment of the invention for assembling and delivering a chain-type pharmaceutical composition to a lumen of a blood vessel.

Fig. 5 schematically shows two versions of a medical storage device comprising a tube for storing a chained pharmaceutical composition according to an embodiment of the invention.

Fig. 6 schematically shows a method of treating blood vessels and perivascular cells according to an embodiment of the invention.

Detailed Description

In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It is apparent, however, to one skilled in the art that the present invention may be practiced without these specific details or with an equivalent design.

Where numerical ranges are disclosed herein, such ranges are continuous, including the minimum and maximum values within the range, and each value therebetween, unless otherwise specified. Further, in the case where the range value refers to an integer, only integers from the minimum to the maximum of the range (inclusive) are included. In addition, in the case where a plurality of range values are provided to describe a certain technical feature, the range values may be combined with each other.

It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. For example, when an element is referred to as being "on," "connected to," or "coupled to" another element, it can be directly on, connected or coupled to the other element or intervening elements may also be present. In contrast, when an element is referred to as being "directly on" … …, "directly connected to" or "directly coupled to" another element, there are no intervening elements present.

As shown in fig. 1, the chain type pharmaceutical composition comprises a head section 1 and a body section 2, the body section 2 being linearly arranged with the head section 1 like two adjacent cars of a train are connected in series. Alternatively, the pharmaceutical composition may be referred to as a chain drug structure, or a chain drug dosage form. When administering the pharmaceutical composition into the body of the patient P, the position of the head segment 1 can be observed by a person (e.g. on the display 11) by means of the apparatus 10. However, the position of the body section 2 cannot be observed by a person or sufficiently clearly by means of the same instrument 10. According to the invention, the position of the body segment 2 can be estimated or inferred from the position of the head segment 1 observed. The chained pharmaceutical composition may further comprise a tail section 3, which can be observed by a human with the aid of the device 10. The body section 2 is sandwiched between a head section I and a tail section 3. The head section 1, the body section 2 and the tail section 3 are linearly arranged and connected in series like three consecutive cars of a train. Thus, the position of the body segment 2 can be estimated or derived from the observed position of the head segment 1 and/or the position of the tail segment 3.

The above arrangement of the head section 1 and the body section 2 may be repeated one or more times to form a (body-head) n structure or a simplified (B-H) n structure. B or body, representing body segment 2; h or head, representing head 1; n is an integer and n.gtoreq.2. Thus, a total of 2n head/body sections may be arranged in series like 2n consecutive cars of a train. In some embodiments, the chained pharmaceutical composition may further include a tail segment 3, which may be observed by a human with the aid of the apparatus 10, to form a tail- (body-head) n structure or a simplified T- (B-H) n structure, where T or tail represents a tail segment; n is an integer, n is an integer and n.gtoreq.2. Thus, 2n +1 head sections/body sections/tail sections are arranged in series like 2n +1 consecutive cars of a train. As shown in fig. 1, the head section 1/tail section 3 located between two body sections 2 may be regarded as the tail section 3 of the previous body section 2 or as the head section 1 of the next body section 2.

In a preferred embodiment, the first part of the chain pharmaceutical composition, which is entered or administered into the patient, is preferably the head segment 1. In other words, the first car of the train is preferably the head section 1. In rare cases, the first car of the train may be a body segment.

As shown in fig. 1, the chain-type pharmaceutical composition may be confined in the lumen of a tubular structure 8 having a longitudinal direction, as if the train were confined in a tunnel. The tubular structure 8 may be a blood vessel 4, a catheter 5 or a combination thereof of a human or animal. By "combination" is meant that the catheter 5 is inserted into the blood vessel 4 and their lumens are connected, joined or extended to each other so as to constitute a continuous channel through which the pharmaceutical composition may pass. Examples of blood vessels 4 include, but are not limited to, arterioles, or blood vessels between an arteriole and its downstream capillaries that supply blood to target cells 40 (e.g., tumor cells 41). As will be described later, the medical device 20 may be used to assemble and deliver a chained pharmaceutical composition into a lumen of a blood vessel. The lumen of the tubular structure 8, whether the vessel 4 or the catheter 5, has an inner diameter (or an inner maximum dimension) at a certain location of the lumen; and any segment 1/2/3 (head, body or tail) is constrained to have the same diameter (or outer maximum dimension) as the inner diameter (or inner maximum dimension) at that location. In other words, segment 1/2/3 at this location would fill the entire space of the lumen at that location. For a given volume of segment 1/2/3, when the lumen is larger at a location, the corresponding segment 1/2/3 at that location may then have a larger diameter, but a smaller length in the lengthwise direction of the lumen.

Examples of the instrument 10 include, but are not limited to, X-ray based imaging devices for Computed Tomography (CT), radiography, and fluoroscopy; an ultrasonic instrument; a Magnetic Resonance Imaging (MRI) device; or any combination thereof.

The head section 1, the body section 2 and the tail section 3 may be independent of each other in the form of gas, liquid, slurry or solid, as long as the body section 2 is not completely dissolved, dispersed or suspended (suspended) into the head section 1 or the tail section 3. For example, the head section 1 and the tail section 3 are independent of each other, such as carbon dioxide, air, nitrogen, oxygen, inert gas or mixtures thereof; is a solution (e.g., aqueous solution) of an iodinated contrast agent, such as ionic compounds of diatrizoate, metrizoate, iophthalate, and iodixanoate; nonionic compounds such as iopamidol, ioxilan (ioxilan), iopromide, iodixanol and ioversol; or any mixture thereof. The pharmaceutical composition of the invention may be injected into blood vessels as a radiopaque or radiolucent contrast agent for use with imaging techniques based on X-ray techniques such as fluoroscopy. Angiography or arteriography is a medical imaging technique used to visualize the interior or lumen of blood vessels and body organs, particularly arteries, veins and ventricles.

The pharmaceutical compositions of the present invention may be used as a radiocontrast agent, a medical contrast agent, for enhancing the visibility of internal body structures under X-ray based imaging techniques such as Computed Tomography (CT), radiography and fluoroscopy. The chain-linked drug structures of the present invention may include iodine or barium compounds and may improve the visibility of the regions, referred to as "contrast enhancement".

Carbon dioxide is commonly used for angiography. CO2 angiography is widely used for vascular imaging and endovascular surgery. CO2 is of low risk because it is natural and does not cause allergy. However, it is preferable to use CO2 under the diaphragm because of the risk of embolism during neurovascular surgery. CO2 is a negative contrast agent because it displaces blood when injected into a blood vessel. Carbon dioxide (CO2) gas may also be used as a contrast agent in the venous circulation to delineate (debrine) the right heart to assess suspected pericardial effusion. The safety and tolerance of carbon dioxide can be ensured by peripheral intravenous injection. CO2 may be used as an intra-arterial contrast agent. CO2 angiography is a very useful diagnostic tool by Digital Subtraction Angiography (DSA), particularly for patients who are allergic to iodinated contrast agents or have impaired renal function. In addition, CO2 may be used to guide various vascular interventional procedures, including angioplasty and stenting, transcatheter embolization, and endovascular Abdominal Aortic Aneurysm (AAA) repair. Since the solubility of CO2 is about 20 times higher than that of oxygen, the amount of gas should be adjusted according to actual needs. When injected into the vessel, the CO2 bubbles will completely dissolve in 2-3 minutes; therefore, a greater amount of CO2 is required. If gas becomes trapped in a large abdominal aneurysm, it may persist, allowing gas exchange between CO2 in the blood and nitrogen; therefore, a smaller amount of CO2 is required. This exchange may lead to intestinal ischemia due to a subconjunctival arterial embolism. Local accumulation of gas bubbles can produce severe gas embolism, particularly in pulmonary arteries.

In some embodiments, head section 1/tail section 3 is a gas such as carbon dioxide; the body section 2 is liquid. These liquids preferably comprise ethanol, e.g. pure ethanol, or ethanol containing a small amount of water, e.g. less than 1%, 0.1% or 0.01% by weight of water. It will be appreciated that when ethanol is in contact with human or animal tissue, more or less additional body fluid may enter the ethanol along with the water. The ethanol may be 0.0001-1 ml.

Therapeutic agents such as basic substances (basic substance) or basic compounds (basic compounds) can be dissolved, suspended or dispersed in ethanol. The ethanol may be basified. Examples of the basic substance or basic agent include, but are not limited to, sodium ethoxide, sodium carbonate, sodium hydrogencarbonate, sodium hydroxide, potassium ethoxide, potassium carbonate, potassium hydrogencarbonate, potassium hydroxide, primary amines, secondary amines, tertiary amines, aliphatic amines, aromatic amines, and the like. Depending on the application and the strength, e.g., alkalinity, of the alkaline material, the alkaline material may be present in the ethanol in an amount of 0.01-20% or more by weight of the ethanol. When C02 is injected into blood, it combines with water to produce carbonic acid. Therefore, carbonic acid is likely to neutralize the alkaline substances in ethanol. In view of this, more alkaline material should be included in the ethanol to compensate for the "loss" caused by carbon dioxide neutralization.

The alkaline substance may be used to kill the cancer cells 40/41. For example, the combination of carbohydrate deficiency to neutralize intratumoral lactic acidosis provides an effective method of controlling tumors. With such a method of local infusion of a basic substance into a tumor, patients can be treated by transarterial chemoembolization (TACE). TACE is a minimally invasive surgical intervention in radiology that serves to limit the blood supply to tumors. It combines chemotherapy with embolization (chemoembolization). For example, small embolic particles coated with chemotherapeutic drugs are selectively injected through a catheter into an artery that supplies directly to the tumor. These particles both block blood supply and induce cytotoxicity, attacking tumors in a variety of ways. The basic ethanol in the body section 2 of the present invention functions similarly to such embolic particles, except that it is used to neutralize intratumoral lactic acidosis in conjunction with glucose deprivation.

In cancer management applications, the chained compositions of the invention (CO2 and/or ethanol) may act as an embolus in addition to blocking the blood supply to the tumor, and may include a component, such as a base substance, that chemically attacks the tumor.

It will be appreciated that the body segment 2 (e.g. ethanol) may carry any suitable chemotherapeutic drug for chemoembolization, such as TACE. The body section 2 may alternatively or additionally carry radiotherapy for unsealed source radiotherapy, such as radioactive embolization or Selective Internal Radiotherapy (SIRT). Embolization is a minimally invasive procedure that prevents blood flow to a body site and effectively constricts or occludes the aneurysm. This procedure is typically performed as an endovascular procedure in an interventional suite (interventional suite) by a radiologist.

Fig. 2 schematically provides one example of a medical device 21 for combining and delivering the chained pharmaceutical compositions of the present invention into a vessel lumen. Which can be passed through a guide wire and catheter into the organ being treated. Digital Subtraction Angiography (DSA) methods are used to locate the correct artery or vein position that gives blood supply to the lesion site. These images are then used as a map for the radiologist to access the correct vessel by selecting the appropriate catheter and/or guidewire, depending on the "shape" of the surrounding anatomy. Once the artificial embolus of the invention is successfully introduced, another set of DSA images may be taken to confirm successful entry, except for CO2 which does not require such confirmation.

The medical device 21 includes a head segment material source 211. A head section material tube 211t, for example a channel in a catheter, is used to deliver the head section material 1 from the head section material source 211 directly into the vascular lumen. Similarly, a body tube 212t (e.g., a channel within a catheter) is used to deliver body segment material 2 from the body segment material source 212 directly into the vessel lumen.

For example, the head segmented material source 211 may be a can or cartridge-like source of CO2, filled with 99.99% laboratory grade CO 2. The CO2 cartridge was filled with high purity gas, with a valve, regulator, gas gauge and metal diaphragm, and a regulator set at 18 psi. Due to the risk of injecting large amounts of CO2, the catheter should not be connected directly to a CO2 cartridge, which contains large amounts of high pressure CO 2. In manual mode, CO2 may be delivered into the blood vessel by a transfusion system (plastic bag system) using, for example, a hand-held syringe. The infusion bag (plastic bag) can be connected to a CO2 cartridge through a 0.2 micron filter. A three-way stopcock between the CO2 cartridge and the infusion bag allows the infusion bag to be filled and emptied with carbon dioxide to expel residual air from the infusion bag.

When a syringe is used, it is preferably filled directly from a CO2 cartridge. Sometimes, CO2 should not be drawn into the syringe, as this may lead to gas contamination. When the syringe was filled with CO2, its pressure was reduced to atmospheric pressure by quickly opening and closing the stopcock. The syringe filled with CO2 with the stopcock open should not be left on the bench before injection because the CO2 in the syringe (CO2 concentration > 99%) is quickly replaced by air (CO2 concentration is only 0.03%).

The rate of CO2 injection depends on the diameter, length, and flow rate of the vessel being imaged or treated. For abdominal aortic angiography or inferior vena cava angiography, 30-40cc of CO2 may be injected. When imaging the aortic branch (abdominal cavity, superior mesenteric artery, renal artery) or lower extremity artery, 20-30cc of CO2 may be used. Due to the low viscosity of the gas, CO2 can be injected through a 3-Fr microcatheter for selective and super-selective angiography as well as for selective arterial embolization.

Sometimes the body segment material 2 is produced in situ by mixing two body segment raw materials 2a and 2 b. The body segments 2a and 2b are then delivered directly from the body segment material sources 212a and 212b into the vessel lumen using two body tubes 212at and 212bt, e.g., two channels within a catheter. The two body segment raw materials 2a and 2b may be miscible or immiscible, and thus the body segment 2 may be made of a homogeneous material or divided into two sub-segments 2a and 2 b. If desired, a tail section material tube 213t, such as a channel within a catheter, may be used to deliver the tail section material 3 directly from the tail section material source 213 into the vessel lumen. Controller 219 controls the timing and amount of material 1,2a, 2b and 3 delivered into the vessel lumen such that the segments are linearly arranged in series within the vessel lumen, as is the case with many train cars, in a material arrangement similar to the sequence, > > >.3-2 b-2a-l-3-2b-2a-l-3-2b-2a-l > >, > >.3/l-2 b-2a-3/1-2b-2a-3/l-2b-2a-l > >, or > >. 3/1-2-3/1-2-3/l-2-l > >.

The design of the medical device 21 as shown in fig. 2 may vary somewhat. Referring to fig. 3, the main catheter 218 is inserted into the lumen of a blood vessel. The head section material tube 211t is connected to the main catheter 218 such that the head section material 1 from the head section material source 211 is delivered through the main catheter 218 into the vessel lumen. Similarly, the body and tail material tubes (212at, 212bt, 213t) are connected to the main tube 218 so that the body segment raw materials 2a, 2b and tail segment material 3 from the material sources 212a, 212b, 213 are delivered into the lumen of the blood vessel through the main tube 218. The medical device 21 as shown in fig. 3 may also be slightly modified. Referring to fig. 4, a portion or all of the head material tube 21lt, the body material tubes 212at, 212bt, and the tail material tube 213t may be removed from the medical device. Once the raw materials 1,2a, 2b, and 3 enter the main conduit 218, a chain configuration will be formed.

Referring to fig. 5, the medical storage device 30 includes a tube 31 (soft or rigid, straight or curved) for sealing and storing the chain type pharmaceutical composition as described above. In some embodiments, the storage device 30 includes one or more valves 32, the valves 32 being located between the head section 1/tail section 3 and the body section 2 and separating the head section 1/tail section 3 and the body section 2 from each other. The valve 32 may remain closed during storage of the pharmaceutical composition. Valve 32 may be opened automatically or manually when desired, and there may be a controlled application of pressure at one end of conduit 31 forcing the chained pharmaceutical composition out the other end of conduit 31 and into the lumen of the conduit or vessel.

As shown in fig. 6, the present invention provides a method of treating blood vessels and cells surrounding the blood vessels. The method comprises (i) providing a chain pharmaceutical composition as described above; (ii) applying the pharmaceutical composition to the patient; (iii) observing the position of the head segment with the aid of an instrument; (iv) the position of the body segment, which cannot be directly observed by a person with the aid of the same instrument, is estimated, inferred, calculated or inferred from the observed head segment positions.

In the foregoing specification, embodiments of the invention have been described with a number of specific details that may vary from implementation to implementation. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. The sole and exclusive indicator of the scope of the invention, and is intended by the applicants to be the scope of the invention, is the literal and equivalent scope of the claims, which are intended to be covered by the specific claims and their subsequent modifications.